subject:(estrogen signaling)

Cornell University

1. Frizzell, Kristine. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.

Degree: PhD, Biochemistry, 2011, Cornell University

► Poly(ADP-ribosyl)ation (PARylation) is an enzymatic reaction whereby ADPribose units from donor NAD+ molecules are covalently attached onto target proteins. The regulation of this reaction is… (more)

▼ Poly(ADP-ribosyl)ation (PARylation) is an enzymatic reaction whereby ADPribose units from donor NAD+ molecules are covalently attached onto target proteins. The regulation of this reaction is overseen by two nuclear enzymes, Poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG), that modify target proteins in the nucleus by the addition and removal, respectively, of ADP-ribose polymers. While PARP-1 has generally been studied with respect to its role in DNA damage repair and cell death pathways, recent studies have revealed a role for PARP-1 in transcriptional regulation. The role of PARG in transcriptional regulation, however, is less characterized. In this study, I have investigated the coordinate patterns of gene regulation by PARP-1 and PARG in vivo using genomic and gene-specific analyses. Specifically, I show that PARP-1 and PARG coordinately regulate global patterns of gene expression by affecting genes in the same direction and with similar magnitudes. Further analysis revealed that PARP-1 and PARG localized to the promoters of both positively and negatively regulated target genes in parallel binding patterns. I also show that PARP-1 and PARG enzymatic activities are required for some, but not all, target genes. My results indicate that PARP-1 and PARG, two nuclear enzymes with opposing enzymatic activities, localize to target promoters and act in a similar, rather than antagonistic, manner to regulate gene expression. In a follow-up study, I have used a novel method known as Global Run-on Sequencing (GRO-seq) to define the role of PARP-1 on the estrogen-regulated transcriptome at the level of the nascent transcript, rather than steady-state mRNA levels. I have produced libraries from MCF-7 cells treated with vehicle or 17[beta]estradiol (E2) under three conditions: (i) a control knockdown; (ii) a control knockdown plus a PARP inhibitor, PJ34; and (iii) a PARP-1 knockdown. I have determined that the estrogen response is highly maintained under PARP-1 knockdown or inhibition. Accordingly, upon estrogen treatment, PARP-1 localization patterns are largely unaffected. However, deeper analyses reveal a small number of genes where PARP-1 knockdown or inhibition reduces the estrogen response at the transcription level (GRO-seq) and at the steady state mRNA level (RT-qPCR). The NAD+ metabolite generated from the PARP-1/PARG reaction, ADPribose (ADPR), is a small molecule ligand that is used by macro domain-containing proteins. The histone variant macroH2A1 is one such protein that has generally been studied with respect to its role in transcriptional repression on the inactive X chromosome. However, recent studies have begun to explore a role for macroH2A1 in autosomal gene regulation, as a transcriptional repressor and a transcriptional activator. Recent results from the Kraus lab have shown that the transcriptional coactivator Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) interacts with the macro domain of macroH2A1 in a ligand-independent manner and shows a similar… Advisors/Committee Members: Kraus, William Lee (chair), Collins, Ruth N. (committee member), Lis, John T (committee member).

Subjects/Keywords: parp-1; gene regulation; estrogen signaling

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APA (6^th Edition):

Frizzell, K. (2011). Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33561

Chicago Manual of Style (16^th Edition):

Frizzell, Kristine. “Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.” 2011. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/33561.

MLA Handbook (7^th Edition):

Frizzell, Kristine. “Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.” 2011. Web. 17 Jan 2021.

Vancouver:

Frizzell K. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/33561.

Council of Science Editors:

Frizzell K. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33561

Cornell University

2. Hah, Nasun. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.

Degree: PhD, Biochemistry, 2011, Cornell University

URL: http://hdl.handle.net/1813/33589

► Estrogens play crucial roles in regulating gene expression in physiological and disease states. Estrogens acts through estrogen receptors (ERs) and their binding sites in genomic… (more)

▼ Estrogens play crucial roles in regulating gene expression in physiological and disease states. Estrogens acts through estrogen receptors (ERs) and their binding sites in genomic DNA to modulate transcription by RNA polymerase II. Although recent gene-specific and genomic analyses have provided considerable information about of estrogen-dependent transcription, many aspects of the estrogen signaling network have not yet been elucidated. The goal of my studies was to uncover new information about the immediate and direct effects of estrogen signaling at the cell membrane, in the cytoplasm, and in the nucleus to elucidate the underlying regulatory networks. First, I investigated an ER transcriptional coregulators, SWI/SNF, an ATPdependent chromatin remodeling complex. I explored the molecular functions of the BAF57 and BAF180 subunits of SWI/SNF using a quantitative proteomic approach called SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture). I found that depletion of BAF57 results in a significant depletion of BAF180 from the SWI/SNF complex without decreasing the total cellular BAF180 levels, resulting in an accumulation of cells in the G2/M phase. Knockdown of BAF57 also causes transcriptional misregulation of cell cycle-related genes involved in the late G2 checkpoint. Collectively, these studies have elucidated the role of BAF57 and BAF180 in the transcriptional control of cell proliferation. Second, I have used GRO-Seq (Global Nuclear Run-On and Massively Parallel Sequencing) to explore the immediate effects of estrogen signaling on the transcriptome of breast cancer cells. I found that estrogen directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein coding genes, estrogen regulates the distribution and activity of all three RNA polymerases, and virtually every class of non-coding RNA that has been described to date. I also identified a large number of previously undetected estrogen-regulated intergenic transcripts, many of which are found proximal to ER[alpha] binding sites. These results provide the most comprehensive measurement of the primary and immediate estrogen effects to date. I expect that genome-wide inferences based on the direct estrogen-regulated transcriptome in combination with estrogen-regulated signaling pathway will be useful for understanding estrogen biology. Advisors/Committee Members: Kraus, William Lee (chair), Collins, Ruth N. (committee member), Lis, John T (committee member).

Subjects/Keywords: estrogen; estrogen receptor; GRO-seq; swi/snf; baf57; baf180; silac; proteomic; enhancer; edc; estrogen signaling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hah, N. (2011). Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33589

Chicago Manual of Style (16^th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/33589.

MLA Handbook (7^th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Web. 17 Jan 2021.

Vancouver:

Hah N. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/33589.

Council of Science Editors:

Hah N. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33589

University of Otago

3. Kőszegi, Zsombor. Restorative effect of estrogen on basal forebrain cholinergic neurons .

Degree: 2011, University of Otago

URL: http://hdl.handle.net/10523/1887

► The basal forebrain cholinergic (BFC) system is one of the most important neurotransmitter systems in the brain. It has received much attention in the past… (more)

▼ The basal forebrain cholinergic (BFC) system is one of the most important neurotransmitter systems in the brain. It has received much attention in the past two decades, primarily for its role in learning, memory, attention and behavior. The BFC system has also been reported to be particularly vulnerable in neurodegenerative diseases, such as in Alzheimer’s disease (AD). The gonadal steroid, estrogen, is an essential contributor in controlling the vulnerability of the BFC system. Besides its classical or genomic mechanism, estrogen is known to have non-classical actions on intracellular signaling pathways. In this study, we investigated the ameliorative effects of estrogen treatment and the role of non-classical estrogen actions on BFC neurons in a neurodegenerative mouse model, in vivo. N-methyl-D-aspartate (NMDA) was injected unilaterally into the substantia innominata - nucleus basalis magnocellularis (SI-NBM) complex of the basal forebrain to elicit cholinergic cell death in the injected area and thus fiber loss in the ipsilateral cortex. An acute treatment of 17β-estradiol (E2) after the NMDA-induced lesion restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. Conversely, it did not have any effect on the cholinergic cell loss in the SI-NBM. The ameliorative action of E2 on cholinergic fiber loss was detected in both intact and gonadectomized young male and female mice, but not in aged animals. The E2-induced cholinergic fiber density restoration was also absent in neuron-specific estrogen receptor α (ERα) knockout mice. Selective blockade of the mitogen activated protein kinase (MAPK) and protein kinase A (PKA) pathways prevented E2’s ability to restore the cholinergic fiber density. Furthermore, activation of non-classical estrogen signaling by a non-classical pathway activator (estren) induced E2-like fiber restoration. Our findings demonstrate that estrogen restores the cholinergic fiber density in the cortex through a non-classical signaling mechanism after the loss of subcortical cholinergic input. Similar restorative effects were observed in young animals, irrespective of sex or endogenous estrogen levels. These observations reveal a critical role for non-classical estrogen signaling via ERα and MAPK-PKA pathways in BFC neurons, in vivo. Taken together, our study discloses important aspects relating to the vulnerability of the BFC system in neurodegenerative processes, such as AD or traumatic brain injury and might shed light on future medical treatments through the use of non-classical estrogen pathway activators. Advisors/Committee Members: Ábrahám, István (advisor).

Subjects/Keywords: estrogen; cholinergic; basal forebrain; neurodegeneration; non-classical; signaling pathway

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kőszegi, Z. (2011). Restorative effect of estrogen on basal forebrain cholinergic neurons . (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/1887

Chicago Manual of Style (16^th Edition):

Kőszegi, Zsombor. “Restorative effect of estrogen on basal forebrain cholinergic neurons .” 2011. Doctoral Dissertation, University of Otago. Accessed January 17, 2021. http://hdl.handle.net/10523/1887.

MLA Handbook (7^th Edition):

Kőszegi, Zsombor. “Restorative effect of estrogen on basal forebrain cholinergic neurons .” 2011. Web. 17 Jan 2021.

Vancouver:

Kőszegi Z. Restorative effect of estrogen on basal forebrain cholinergic neurons . [Internet] [Doctoral dissertation]. University of Otago; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10523/1887.

Council of Science Editors:

Kőszegi Z. Restorative effect of estrogen on basal forebrain cholinergic neurons . [Doctoral Dissertation]. University of Otago; 2011. Available from: http://hdl.handle.net/10523/1887

Texas A&M University

4. Yoo, Gyhye. Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer.

Degree: PhD, Nutrition, 2015, Texas A&M University

URL: http://hdl.handle.net/1969.1/156457

► Estrogen is a female sex hormone that has a variety of biologic actions via modulation of gene expression through estrogen receptors (ERs). The protective effect… (more)

Subjects/Keywords: Estrogen Signaling; Phytoestrogens; Colitis; Colon Cancer; IL-6; p53

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yoo, G. (2015). Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/156457

Chicago Manual of Style (16^th Edition):

Yoo, Gyhye. “Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer.” 2015. Doctoral Dissertation, Texas A&M University. Accessed January 17, 2021. http://hdl.handle.net/1969.1/156457.

MLA Handbook (7^th Edition):

Yoo, Gyhye. “Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer.” 2015. Web. 17 Jan 2021.

Vancouver:

Yoo G. Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer. [Internet] [Doctoral dissertation]. Texas A&M University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1969.1/156457.

Council of Science Editors:

Yoo G. Influence of Estradiol and Phytoestrogens on Colitis and Colon Cancer. [Doctoral Dissertation]. Texas A&M University; 2015. Available from: http://hdl.handle.net/1969.1/156457

University of Houston

5. Hao, Ruixin 1983-. Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption.

Degree: PhD, Cell and Molecular Biology, University of Houston

URL: http://hdl.handle.net/10657/3403

► Estrogen signaling, mediated by estrogen receptors (ERs) and G-protein-coupled estrogen receptor (GPER), plays important roles in humans and wildlife. Perturbing estrogen signaling may lead to… (more)

▼ Estrogen signaling, mediated by estrogen receptors (ERs) and G-protein-coupled estrogen receptor (GPER), plays important roles in humans and wildlife. Perturbing estrogen signaling may lead to deleterious health problems such as infertility, developmental defects, metabolic disorders, and certain types of cancers. A broad range of chemicals, which are classified as estrogenic endocrine disruptors (EEDs), can bind to ERs or GPERs, thereby interfering with estrogen signaling and causing adverse effects. Zebrafish embryos/larvae are an emerging model used in xenoestrogen studies. However, endogenous estrogen signaling in developing zebrafish embryos/larvae is still poorly understood. In the studies of this dissertation, first a whole-genome analysis of estrogen regulated genes in zebrafish embryos/larvae at different developmental stages was performed. The identified estrogen-responsive genes were distinct between the four time points, however GO biological process enrichment of the estrogen-responsive genes revealed similar functional groups between the four time points. Tissue-specific effects of estrogen were also analyzed using tissue enrichment of estrogen-responsive genes and Tg(5xERE:GFP) transgenic fish. Brain, liver, heart, and pancreas were major estrogen-responsive organs in developing embryos and adults. Several candidate biomarkers were suggested from our studies, including f13a1a, cpn1, and zp3. Second, estrogenic and anti-estrogenic effects of ten bisphenols were assessed using zebrafish larvae. Selected estrogen-responsive genes identified from transcriptome analysis were tested in wild-type zebrafish larvae exposed to these bisphenols. Transgenic reporter fish Tg(5xERE:GFP) were used to study the tissue specific effects of the selected bisphenols and GFP quantification was used to compare the estrogenic effects of the bisphenols. Anti-estrogenic effects of the bisphenols were also studied in zebrafish larvae. Eight bisphenols showed tissue-specific and dose-dependent estrogenic effects in zebrafish larvae. One bisphenol showed only anti-estrogenic effects, and one bisphenol showed neither estrogenic nor anti-estrogenic effects. f13a1a was shown to be an effective new biomarker for assessing estrogenicity of chemicals. Third, high throughput screening of ToxCastTM Phase I pesticides library and NIH Clinical Collection drug library was performed using Tg(5xERE:GFP) reporter fish. A total of 26 environmental estrogens and 62 clinical drugs with estrogenic activities were identified from these two libraries. Then environmental estrogens identified from reporter zebrafish assays were compared to xenoestrogen datasets from in vitro assays, which are maintained in ToxCast Database (ToxCastDB). Seven chemicals were overlapping between our fish assays and all of the in vitro assays in ToxCastDB. In conclusion, zebrafish embryos/larvae are shown to be a good model for studying estrogen signaling and estrogenic endocrine disruption. These studies are important for understanding estrogen signaling in developing… Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Bondesson, Maria (committee member), Williams, Cecilia M. (committee member), Sater, Amy K. (committee member), Wagner, Daniel (committee member).

Subjects/Keywords: Zebrafish; Estrogen signaling; Endocrine disruption

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APA (6^th Edition):

Hao, R. 1. (n.d.). Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/3403

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16^th Edition):

Hao, Ruixin 1983-. “Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption.” Doctoral Dissertation, University of Houston. Accessed January 17, 2021. http://hdl.handle.net/10657/3403.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7^th Edition):

Hao, Ruixin 1983-. “Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption.” Web. 17 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Hao R1. Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10657/3403.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Hao R1. Zebrafish as a Model for Studying Estrogen Signaling and Estrogenic Endocrine Disruption. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/3403

Note: this citation may be lacking information needed for this citation format:
No year of publication.

University of Houston

6. Mesmar, Fahmi 1983-. Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors.

Degree: PhD, Biology, 2017, University of Houston

URL: http://hdl.handle.net/10657/4553

► Colorectal and pancreatic cancers are predominant gastrointestinal (GI) tumors with estimated 90,970 deaths in the United Sates in 2016, representing ~ 60% of the total… (more)

▼ Colorectal and pancreatic cancers are predominant gastrointestinal (GI) tumors with estimated 90,970 deaths in the United Sates in 2016, representing ~ 60% of the total GI tumors related-mortalities. Several investigations, including meta-analysis, preclinical, and in vitro studies have established the protective role of estrogens and related receptors against GI tumors. The main estrogen nuclear receptor in the colon is estrogen receptor beta (ERβ/ESR2). During colon cancer progression, ERβ expression is considerably reduced. Re-expressing ERβ in colon cancer cell line (SW480) induces significant changes in miRnome. miR-205 is among the upregulated genes which directly targets the oncogene PROX1. In vivo studies demonstrated that both ERβ and miR-205 exert anti-metastatic effects. SW620, a highly metastasized human colorectal cancer cell line was used for further analysis. This cell line dose not express any ERα or ERβ, and ERβ was introduced using lentiviral. Here we show that 17β-estradiol (E2) has an ERβ-dependent as well as ERβ-independent effects suggesting possible role of alternative receptors in estrogen signaling in colonic epithelium such as G-protein coupled estrogen receptor 1 (GPER1). In response to E2 or GPER1-selective agonist G1 treatments, several oncogenic long non-coding RNAs (lncRNAs) show downregulation, including MALAT1, NEAT1, ZEB1-AS1 and HOTAIR. Several of these lncRNAs are involved in epithelial-to-mesenchymal transition (EMT) and tumor metastasis. Collectively, our data demonstrate that estrogen singling in the colon has anti-metastatic effects by modulating the expression of the cancer-related noncoding RNAs. EMT transition is frequently linked to a chemoresistance phenotype, which is a common phenomenon in pancreatic cancer. Genistein, a phytoestrogen, has a chemoenhancing effect when it combined with gemcitabine in pancreatic cancer cell lines (PANC1 and MiaPaCa2). Using RNA-seq, genistein induces expression of genes that are related to apoptosis, calcium signaling, and endoplasmic reticulum stress, which can all be linked to enhanced GPER1 activity. Genistein treatment also reduces the expression of several inflammation related genes including MUC1. We demonstrate that G1 treatment similarly reduces proliferation, but dose not fully mimic the apoptotic features of genistein. Collectively, these data indicate that using an estrogenic compound, such as genistein, may enhance the anti-proliferative and apoptotic effects of chemotherapeutic agents such as gemcitabine. Advisors/Committee Members: Chung, Sang-Hyuk (advisor), Williams, Cecilia M. (advisor), Khurana, Seema (committee member), Lin, Chin-Yo (committee member), Bondesson, Maria (committee member), Zhao, Chunyan (committee member).

Subjects/Keywords: Gastrointestinal cancers; Estrogen signaling; Tumor metastasis; ERB; GPER1; Noncoding RNAs

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mesmar, F. 1. (2017). Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4553

Chicago Manual of Style (16^th Edition):

Mesmar, Fahmi 1983-. “Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors.” 2017. Doctoral Dissertation, University of Houston. Accessed January 17, 2021. http://hdl.handle.net/10657/4553.

MLA Handbook (7^th Edition):

Mesmar, Fahmi 1983-. “Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors.” 2017. Web. 17 Jan 2021.

Vancouver:

Mesmar F1. Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors. [Internet] [Doctoral dissertation]. University of Houston; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10657/4553.

Council of Science Editors:

Mesmar F1. Deciphering the Molecular Mechanisms of Estrogen Signaling in Gastrointestinal Tumors. [Doctoral Dissertation]. University of Houston; 2017. Available from: http://hdl.handle.net/10657/4553

University of Western Ontario

7. Fortunato, Jenna H. The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2.

Degree: 2020, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/7391

► Women are more likely to have severe asthma than men. Recent data suggest this could be due to women having more circulating CD4+CRTh2+ T cells… (more)

Subjects/Keywords: Asthma; CRTh2; Estrogen signaling; Genetic variation; Glucocorticosteroid; Th2 inflammation; Immunopathology

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APA (6^th Edition):

Fortunato, J. H. (2020). The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/7391

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fortunato, Jenna H. “The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2.” 2020. Thesis, University of Western Ontario. Accessed January 17, 2021. https://ir.lib.uwo.ca/etd/7391.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fortunato, Jenna H. “The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2.” 2020. Web. 17 Jan 2021.

Vancouver:

Fortunato JH. The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2. [Internet] [Thesis]. University of Western Ontario; 2020. [cited 2021 Jan 17]. Available from: https://ir.lib.uwo.ca/etd/7391.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fortunato JH. The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of CRTh2. [Thesis]. University of Western Ontario; 2020. Available from: https://ir.lib.uwo.ca/etd/7391

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Duke University

8. Miller, Hilary Dawn. The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) .

Degree: 2011, Duke University

URL: http://hdl.handle.net/10161/5709

► Endocrine disrupting chemicals (EDCs) are ubiquitous and often act as xenoestrogens with the ability to disrupt estrogen signaling through differential binding to the various… (more)

▼ Endocrine disrupting chemicals (EDCs) are ubiquitous and often act as xenoestrogens with the ability to disrupt estrogen signaling through differential binding to the various estrogen receptors. Exposure to these xenoestrogens has led to detrimental effects on male reproduction. In fish, observed effects include sex reversal, presence of testicular oocytes, altered courting behavior, vitellogenin synthesis in males, altered fertility and gonadal histopathology. Understanding how xenoestrogens exert their effects is complicated by the existence of multiple estrogen receptors (ESR1, ESR2a, ESR2b, and GPER), coupled with their ability for crosstalk and differential binding capability of selective estrogen receptor modulators (SERMS). Additionally, estrogen can signal through both classic genomic signaling and nongenomic signaling. Furthermore, the importance of estrogen signaling in normal male reproduction is just beginning to be understood. The primary goal of this dissertation was to assess the implications of aberrant estrogen signaling on male reproductive capacity, testicular morphology and gene expression changes in the small aquarium model fish, medaka, by investigating effects of a general estrogen receptor agonist, ethinylestradiol (EE2), and those of a G-protein estrogen receptor (GPER) specific agonist, G-1. This was assessed through breeding experiments, histological assessment of testicular morphology and microarray assessment of testicular gene expression changes following exposure to EE2 and G-1. Finally, a comparison of altered testicular morphology between EE2 and G-1 induced changes was further assessed using a variety of histological techniques. The findings demonstrate that a 14-day exposure to EE2 impaired male reproductive capacity and altered testicular morphology and gene expression in a time- and dose-dependent manner. The testicular morphologic alterations observed include increased germ cell apoptosis, decreased germinal epithelium and thickening of the interstitium. These morphologic changes were highly associated with gene expression changes. A pathway analysis of the differentially expressed genes emphasized genes and pathways associated with apoptosis, cell proliferation, collagen production/extracellular matrix organization, and protein ubiquitination among others. Comparatively, a 14-day exposure to G-1 did not affect male reproductive capacity but did alter testicular morphology and gene expression. The histological analysis found an increased cellularity of the interstitium leading to thickened interstitium but no change in germinal epithelium. The microarray data indicate differential expression in genes most commonly involved in cell cycle, cell proliferation, apoptosis, transcription, translation, and ubiquitination. Finally, an assessment of the testicular histological phenotypes following EE2 and G-1 exposure indicate different morphologic changes led to thickened interstitium observed in the two exposures. In EE2 exposed fish, thickening of interstitium was associated with… Advisors/Committee Members: Hinton, David E (advisor).

Subjects/Keywords: Toxicology; Environmental Health; estrogen signaling; gene expression; medaka; reproduction; testis; toxicology

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APA (6^th Edition):

Miller, H. D. (2011). The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/5709

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Miller, Hilary Dawn. “The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) .” 2011. Thesis, Duke University. Accessed January 17, 2021. http://hdl.handle.net/10161/5709.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Miller, Hilary Dawn. “The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) .” 2011. Web. 17 Jan 2021.

Vancouver:

Miller HD. The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) . [Internet] [Thesis]. Duke University; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10161/5709.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Miller HD. The Influence of Estrogen Signaling on Male Reproduction in Medaka (Oryzias latipes) . [Thesis]. Duke University; 2011. Available from: http://hdl.handle.net/10161/5709

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Duke University

9. Schwabe, Jennifer Link. Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes .

Degree: 2017, Duke University

URL: http://hdl.handle.net/10161/14487

► Lysine-specific demethylase 1 (LSD1/KDM1A) regulates transcriptional events by post-translational modifications of histone H3 tails at residues K4 an K9. This enzyme plays a vast… (more)

▼ Lysine-specific demethylase 1 (LSD1/KDM1A) regulates transcriptional events by post-translational modifications of histone H3 tails at residues K4 an K9. This enzyme plays a vast number of roles in both normal cellular functions and diseases states. Increasingly it is appreciated that this enzyme, like most epigenetic regulators, does not function alone, but rather forms a catalytic subunit of much larger protein assemblies that congregate on chromatin to concertedly mediate transcriptional events. LSD1 in particular has been found in many different complexes, in many different tissues and can facilitate both activation and repression events. Because of these roles, LSD1 is viewed as a potential therapeutic target. Significant effort has recently led to the development of highly selective and potent active-site inhibitors. These inhibitors have particularly shed light on the cancer-promoting activities of LSD1 in acute myeloid leukemia and small cell lung carcinoma. However, one failing of these strategies is that active site inhibition is incapable of differentiating between the multitude of functions LSD1 performs. We sought to address this issue by instead developing first-generation tools to explore protein-protein interaction disruption as an alternative strategy for inhibiting the enzyme. To this end, we have carefully examined a well-characterized interaction between LSD1 and the scaffolding protein CoREST. Using this interaction as a template, we developed a probe we show can compete with CoREST for interaction with LSD1. Furthermore, we generated cell permeable versions of this probe and examined the effects in a model of breast cancer. We find that our probe can selectively inhibit estrogen signaling, a feat that was not possible with current small molecule inhibition or RNA interference technologies. We therefore we propose that disrupting interactions such as this is an excellent alternative for targeting “undruggable” proteins, but also may also expand the current therapeutic space by granting precise control over the individual functions of proteins. Advisors/Committee Members: McCafferty, Dewey G (advisor).

Subjects/Keywords: Biochemistry; Cellular biology; CoREST; Estrogen Signaling; KDM1A; LSD1; Protein-protein interaction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schwabe, J. L. (2017). Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/14487

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Schwabe, Jennifer Link. “Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes .” 2017. Thesis, Duke University. Accessed January 17, 2021. http://hdl.handle.net/10161/14487.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Schwabe, Jennifer Link. “Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes .” 2017. Web. 17 Jan 2021.

Vancouver:

Schwabe JL. Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes . [Internet] [Thesis]. Duke University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10161/14487.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Schwabe JL. Targeting Protein-Protein Interactions for Disruption of LSD1 (KDM1A) Complexes . [Thesis]. Duke University; 2017. Available from: http://hdl.handle.net/10161/14487

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Kansas State University

10. Souza, Samson Aeloa. Protein-ligand interactions of druggable protein targets.

Degree: PhD, Biochemistry and Molecular Biophysics Interdepartmental Program, 2020, Kansas State University

URL: http://hdl.handle.net/2097/40598

► A druggable protein target is one in which an exogenous ligand will induce the desired response. In this work, small molecule interactions of three druggable… (more)

▼ A druggable protein target is one in which an exogenous ligand will induce the desired response. In this work, small molecule interactions of three druggable protein targets will be detailed. The first of these is a bacterial enzyme involved in the synthesis of cofactor biotin, which is an essential cofactor exploited across all life domains. It is necessary for fatty acid biosynthesis, gluconeogenesis, and amino acid metabolism. Mammals lack the biosynthetic machinery to produce it and must acquire it in the diet. Meanwhile, bacteria such as E. coli, and M. tuberculosis can synthesize it endogenously. As such, enzymes involved in biotin synthesis are attractive targets in antimicrobial development. Diaminopelargonic acid synthase (BioA) catalyzes the second step in the conserved pathway from starting compounds pimeloyl-CoA and L-alanine. Unlike other bacteria, Bacillus subtilis requires L-lysine as a substrate for transamination of 7-keto-8-aminopelargonic acid (KAPA) to its diamino-product, 7,8-diaminopelargonic acid (DAPA), by BioA. I present kinetic work that suggests a donation of lysine ε-amino group to KAPA. I follow this with the crystal structure of PLP-conjugated lysine as an external aldimine (LLP). The adduct is stabilized by electrostatic interactions between the carboxylate and R410, and pi-cation interactions between the former lys α-amine and two aromatic side chains in the pocket. In the latter segment of this work, I survey ligand interactions of two membrane proteins directly involved in estrogen signaling. The first of these two proteins, G-protein coupled estrogen receptor (GPER), is localized in the endoplasmic reticulum. This research, which was the first to demonstrate in vitro ligand binding with recombinant protein, focuses on steps to produce functional GPER for structural and binding assays. GPER is a potential non-nuclear strategy for breast cancer therapy since 10 – 20 % of diagnoses are estrogen receptor negative. The second estrogen-related protein I will explore is the cytochrome P450 enzyme aromatase (Cyp19). It catalyzes the last biosynthetic step in the production of endogenous estrogens in mammals. To this end, it is a current target in the treatment of hormone-related illnesses and diseases such as endometriosis, ovarian cancer, and breast cancer. Current aromatase inhibitors (AIs), for instance, tamoxifen, are potent, yet they often lead to debilitating side effects. Eventual relapse creates a need for novel breast cancer therapeutics that improve patient outcome. Virtual screening of a library of millions of compounds is often employed to initially uncover drug candidates. I provide activity data of these top hit candidates against a putative Cyp19 allosteric site. Two lead compounds, AR11 and AR13, exhibit potent, anti-aromatase activity comparable to active tamoxifen metabolite, endoxifen. Inhibitory mechanisms of these compounds and the journey to find a promising construct for cocrystallization will be explored. This insight will aid in the search to unearth a novel class… Advisors/Committee Members: Major Professor Not Listed.

Subjects/Keywords: Estrogen signaling; Aromatase Inhibitor (AI); Breast Cancer target

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Souza, S. A. (2020). Protein-ligand interactions of druggable protein targets. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/40598

Chicago Manual of Style (16^th Edition):

Souza, Samson Aeloa. “Protein-ligand interactions of druggable protein targets.” 2020. Doctoral Dissertation, Kansas State University. Accessed January 17, 2021. http://hdl.handle.net/2097/40598.

MLA Handbook (7^th Edition):

Souza, Samson Aeloa. “Protein-ligand interactions of druggable protein targets.” 2020. Web. 17 Jan 2021.

Vancouver:

Souza SA. Protein-ligand interactions of druggable protein targets. [Internet] [Doctoral dissertation]. Kansas State University; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2097/40598.

Council of Science Editors:

Souza SA. Protein-ligand interactions of druggable protein targets. [Doctoral Dissertation]. Kansas State University; 2020. Available from: http://hdl.handle.net/2097/40598

Freie Universität Berlin

11. Kornhuber, Marja. Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties.

Degree: 2020, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-27471

► Das endokrine System ist ein zentraler Bestandteil während der Entwicklung und sowie der Regulierung physiologischer Prozesse im menschlichen Körper. Eine Dysregulation des endokrinen Systems steht… (more)

▼ Das endokrine System ist ein zentraler Bestandteil während der Entwicklung und sowie der Regulierung physiologischer Prozesse im menschlichen Körper. Eine Dysregulation des endokrinen Systems steht in Verbindung mit der Entwicklung verschiedener Krankheiten einschließlich Krebs. Vom Menschen hergestellte Chemikalien, die in der Lage sind, das endokrine System zu stören und dadurch nachteilige Auswirkungen auf die Gesundheit haben (als endokrin wirkende Chemikalien (EDC) bezeichnet), geben daher Anlass zur Sorge. Verfügbare in-vitro-Assays, mit denen EDCs identifiziert und charakterisiert werden können, liefern hauptsächlich Informationen über Mechanismen und Wege der endokrinen Aktivität. Diese Assays decken jedoch in der Regel keine funktionellen Endpunkte ab, die eine Vorhersage zur Krankheitsentwicklung wie hormonbedingte Tumorbildung ermöglichen. Daher müssen komplexe in-vivo-Studien durchgeführt werden, für die eine große Anzahl von Testtieren erforderlich ist. In dieser Arbeit wird der E-Morph-Assay vorgestellt: eine neue robuste und prädiktive in-vitro-Testmethode, mit der Chemikalien identifiziert werden können, die den Östrogensignalweg stören. Die Entwicklung dieses Assays basiert auf der Feststellung, dass der Östrogensignalweg die Organisation von Adherens Junctions (AJ) in der menschlichen MCF7 Brustkrebszelllinie verändert. Die Spezifität dieses Effekts für den Östrogenrezeptor α (ERα) Signalweg konnte durch Inhibitions- und Knock-Down-Studien verifiziert werden, während die Modulation des G-Protein-gekoppelten Östrogenrezeptors 1 (GPER1) keinen Einfluss hatte. Es konnte gezeigt werden, dass die AJ-Reorganisation durch das ERα-Zielgen Amphiregulin (AREG) vermittelt wird. Zusätzlich sind der epidermalen Wachstumsfaktor Rezeptor (EGFR) und nachgeschaltete Kinase-Signalwege der RhoA- und Src-Familie beteiligt. Diese krebsrelevanten Signalwege unterstützen die mechanistische und klinische Relevanz der AJ-Organisation als neuen funktionellen Endpunkt im E-Morph-Assay. Die Entwicklung einer Pipeline für die automatisierte Bilderfassung und quantitative Bildanalyse ermöglicht das schnelle Analysieren von Chemikalien. Das Testen von 17 Referenzchemikalien mit bekannten östrogenen Eigenschaften zeigte eine hohe Vorhersagekapazität des E-Morph-Assays. Advisors/Committee Members: female (gender), Schönfelder, Gilbert (firstReferee), Sigrist, Stephan (furtherReferee).

Subjects/Keywords: Breast cancer; endocrine disruptors; estrogens; estrogen signaling; test method; cell morphology; ddc:572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kornhuber, M. (2020). Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-27471

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kornhuber, Marja. “Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties.” 2020. Thesis, Freie Universität Berlin. Accessed January 17, 2021. http://dx.doi.org/10.17169/refubium-27471.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kornhuber, Marja. “Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties.” 2020. Web. 17 Jan 2021.

Vancouver:

Kornhuber M. Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties. [Internet] [Thesis]. Freie Universität Berlin; 2020. [cited 2021 Jan 17]. Available from: http://dx.doi.org/10.17169/refubium-27471.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kornhuber M. Development and Characterization of a Predictive Cell-based Test Method for the Identification of Substances with Estrogenic Properties. [Thesis]. Freie Universität Berlin; 2020. Available from: http://dx.doi.org/10.17169/refubium-27471

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota

12. Peterson, Brittni. From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females.

Degree: PhD, Neuroscience, 2016, University of Minnesota

URL: http://hdl.handle.net/11299/182178

► Drug addiction is a widespread condition affecting 8-10% of the population nationwide. Although men and women are both affected by drug addiction, sex-differences in responsiveness… (more)

▼ Drug addiction is a widespread condition affecting 8-10% of the population nationwide. Although men and women are both affected by drug addiction, sex-differences in responsiveness to drugs of abuse are apparent, with women showing a greater sensitivity than men. For over 30 years, the ovarian hormone estradiol has been recognized as a key biological factor contributing to the development of drug addiction in females, with little understanding of the neurobiological underpinnings. Here we propose a neural mechanism through which estradiol primes females to respond more strongly to drugs of abuse. Estradiol can act at intracellular or membrane-localized estrogen receptors to influence cellular function. Exclusively in females, a subset of these membrane estrogen receptors are coupled to group I metabotropic glutamate receptors (mGluRs). We demonstrate that it is through group I mGluRs that estradiol structurally remodels reward circuits in the nucleus accumbens (NAc), an effect associated with heightened sensitivity to drugs of abuse in females. In the nervous system, both estradiol and group I mGluRs can influence the activity of the endogenous cannabinoid (endoCB) system, an emerging mediator of neural plasticity and behavioral responses to drugs of abuse. Interestingly, we find that estradiol enhances the activity of the endoCB system in the female NAc by rapidly altering concentrations of the two best known endoCBs and increasing cannabinoid receptor expression. Further we demonstrate that activation of the endoCB system is critical for estradiol to induce structural plasticity in the NAc and facilitate behavioral responses to repeated drug exposure. Collectively, our results suggest that estradiol, group I mGluRs and the endoCB system may be linked through a serial pathway that is principally important in female drug addiction. These findings begin to elucidate a neural mechanism underlying female vulnerability to addiction that contributes to sex differences in drug abuse and may actually provide putative therapeutic targets that are particularly effective in treating drug abuse in women.

Subjects/Keywords: drugs of abuse; endocannabinoids; medium spiny neurons; membrane estrogen signaling; metabotropic glutamate receptors; nucleus accumbens

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Peterson, B. (2016). From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/182178

Chicago Manual of Style (16^th Edition):

Peterson, Brittni. “From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females.” 2016. Doctoral Dissertation, University of Minnesota. Accessed January 17, 2021. http://hdl.handle.net/11299/182178.

MLA Handbook (7^th Edition):

Peterson, Brittni. “From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females.” 2016. Web. 17 Jan 2021.

Vancouver:

Peterson B. From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females. [Internet] [Doctoral dissertation]. University of Minnesota; 2016. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/11299/182178.

Council of Science Editors:

Peterson B. From Estradiol to the Endogenous Cannabinoid System: A Gateway to Drug Addiction in Females. [Doctoral Dissertation]. University of Minnesota; 2016. Available from: http://hdl.handle.net/11299/182178

Université Montpellier II

13. Gamba, Laurent. Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system.

Degree: Docteur es, Biologie Santé, 2010, Université Montpellier II

URL: http://www.theses.fr/2010MON20085

►

La ligne latérale postérieure embryonnaire du poisson-zèbre est composée d'un ensemble d'organes sensoriels, appelés neuromastes, qui permet au poisson de détecter les mouvements de l'eau.… (more)

▼

La ligne latérale postérieure embryonnaire du poisson-zèbre est composée d'un ensemble d'organes sensoriels, appelés neuromastes, qui permet au poisson de détecter les mouvements de l'eau. Le primordium qui génère la ligne latérale postérieure embryonnaire migre de la tête vers l'extrémité de la queue le long d'une piste de cellules sécrétrices de SDF-1, et dépose des groupes de cellules précurseurs des neuromastes. Cette migration dépend de la présence de CXCR4, le récepteur de SDF-1, dans la région en tête du primordium et de la présence du second récepteur de SDF-1, CXCR7, dans la région en queue du primordium. L'objectif de ma thèse est d'identifier des régulateurs de l'expression de cxcr4b au sein du primordium. Nous avons montré que l'inactivation du récepteur des strogènes ESR1 induit l'expression ectopique de cxcr4b dans les cellules de queue du primordium alors que sa surexpression induit une réduction du domaine d'expression de cxcr4b, suggérant que ESR1 agit comme un répresseur de cxcr4b. Cette découverte expliquerait pourquoi les strogènes diminuent la capacité métastatique des cellules du cancer du sein strogéno-dépendants. L'inactivation de ESR1 conduit aussi à l'extinction de l'expression de cxcr7b dans les cellules de queue du primordium, cet effet étant toutefois indirect et induit par la signalisation ectopique SDF-1/CXCR4 dans ces cellules. L'inactivation et la surexpression de ESR1 provoquent toutes deux une migration défectueuse du primordium, confirmant l'importance de ce récepteur dans le contrôle de la migration dépendante de SDF-1. Nous avons aussi montré qu'un effecteur majeur de la signalisation Wnt canonique, LEF-1, contribue au contrôle de l'expression de cxcr4b et de cxcr7b dans les cellules en tête du primordium. Nous montrons que la prolifération cellulaire, qui assure une taille constante du primordium en dépit des dépositions successives de cellules, est réduite en absence de LEF-1, et que cela conduit à une ligne latérale postérieure incomplète.

The zebrafish embryonic posterior lateral line is componed by a set sense organs, called neuromasts, allowing the fish to detect the water movements. The primordium that generates the embryonic posterior lateral line of zebrafish migrates from the head to the tip of the tail along a trail of SDF-1-producing cells, and deposits cell groups that will become the neuromasts. This migration critically depends on the presence of the SDF-1 receptor CXCR4 in the leading region of the primordium and on the presence of a second SDF1 receptor, CXCR7, in the trailing region of the primordium. The aim of my thesis is to identify regulators of the cxcr4b expression within the primordium. Here we show that inactivation of the estrogen receptor ESR1 results in ectopic expression of cxcr4b throughout the primordium, whereas ESR1 overexpression results in a reciprocal reduction in the domain of cxcr4b expression, suggesting that ESR1 acts as a repressor of cxcr4b. This finding could explain why estrogens significantly decrease the metastatic ability of…

Advisors/Committee Members: Dambly-Chaudière, Christine (thesis director).

Subjects/Keywords: Migration cellulaire collective; Primordium; Cxcr7; Récepteur des strogènes; Transgénèse; Signalisation Wnt; Collective cell migration; Primordium; Cxcr7; Estrogen receptor; Transgenesis; Wnt signaling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gamba, L. (2010). Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2010MON20085

Chicago Manual of Style (16^th Edition):

Gamba, Laurent. “Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system.” 2010. Doctoral Dissertation, Université Montpellier II. Accessed January 17, 2021. http://www.theses.fr/2010MON20085.

MLA Handbook (7^th Edition):

Gamba, Laurent. “Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system.” 2010. Web. 17 Jan 2021.

Vancouver:

Gamba L. Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system. [Internet] [Doctoral dissertation]. Université Montpellier II; 2010. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2010MON20085.

Council of Science Editors:

Gamba L. Etude de la régulation du gène codant le récepteur de chimiokine CXCR4 dans le système de la ligne latérale postérieure du poisson-zèbre (danio rerio) : Study of the regulation of the gene encoding the chemokine receptor CXCR4 in the zebrafish (danio rerio) posterior lateral line system. [Doctoral Dissertation]. Université Montpellier II; 2010. Available from: http://www.theses.fr/2010MON20085

University of Western Ontario

14. Kolendowski, Bart. The Role of Thymine-DNA Glycosylase In Transcriptional Regulation.

Degree: 2018, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/5285

► Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is… (more)

▼ Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is a base excision repair protein and a coregulator that has been implicated in a diverse set of fundamental biological processes including embryonic development, nuclear receptor signaling and Wnt signaling. Importantly, TDG has been shown to play an important role in transcriptional regulation in a wide variety of systems. Details surrounding the mechanism through which TDG acts remain unclear. In this thesis we explore the role of TDG in Estrogen Receptor (ER)-dependent signaling and in cellular senescence. To characterize the role of TDG in ER mediated signaling we first mapped β-Estradiol (E2)-dependent DNA binding of TDG in the MCF7 breast cancer cell line using ChIP-Seq. Using bioinformatics in conjunction with more traditional biochemistry techniques I established that a significant component of TDG binding occurs at enhancers, where it was able to mediate the production of enhancer RNA (eRNA) and 3-dimensional reorganization of transcriptional units. Knockdown of TDG disrupts E2-mediated upregulation of ER-targets and inhibits growth. Remarkably, in addition to behavior mimicking that of an oncogene, I find that TDG knockdown and depletion result in a much more aggressive phenotype, revealing its role as a potential potent tumor suppressor. To explore the role of TDG in cellular senescence we induced senescence in IMR90 human fibroblasts using hydrogen peroxide (H2O2) and monitored markers of senescence, including proliferation and β-galactosidase staining. I found that while senescence was readily inducible in this cell line using H2O2, knockdown of TDG was able to significantly impede the process. Using ChIP, I found that TDG was recruited to a CpG island overlapping the CDKN2A promoter, a tumor suppressor important for senescence. Further studies including ChIP, bisulfite sequencing and conventional assays revealed that TDG is required for H2O2-mediated transcription of CDKN2A in a CBP-dependent and active-demethylation independent manner. Collectively, these studies extend the role of TDG in transcriptional regulation, implicating it as a mediator of cellular senescence and as a mediator of eRNA transcription and 3-dimensional re-organization in hormone signaling.

Subjects/Keywords: Thymine DNA Glycosylase; Estrogen signaling; Senescence; Cancer; Enhancers; eRNA; Biochemistry, Biophysics, and Structural Biology; Bioinformatics; Cancer Biology; Genetics and Genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kolendowski, B. (2018). The Role of Thymine-DNA Glycosylase In Transcriptional Regulation. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/5285

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kolendowski, Bart. “The Role of Thymine-DNA Glycosylase In Transcriptional Regulation.” 2018. Thesis, University of Western Ontario. Accessed January 17, 2021. https://ir.lib.uwo.ca/etd/5285.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kolendowski, Bart. “The Role of Thymine-DNA Glycosylase In Transcriptional Regulation.” 2018. Web. 17 Jan 2021.

Vancouver:

Kolendowski B. The Role of Thymine-DNA Glycosylase In Transcriptional Regulation. [Internet] [Thesis]. University of Western Ontario; 2018. [cited 2021 Jan 17]. Available from: https://ir.lib.uwo.ca/etd/5285.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kolendowski B. The Role of Thymine-DNA Glycosylase In Transcriptional Regulation. [Thesis]. University of Western Ontario; 2018. Available from: https://ir.lib.uwo.ca/etd/5285

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Guelph

15. Black, Alicia. Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes.

Degree: MS, Department of Human Health and Nutritional Sciences, 2020, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/21267

► Integrin alpha1beta1 protects against OA development when it is upregulated in the early stages of disease development. One possible mechanism through which integrin alpha1beta1 affords… (more)

Subjects/Keywords: integrin; epidermal growth factor receptor; estrogen receptor; cartilage; chondrocyte; osteoarthritis; cell signaling; murine; immunohistochemistry; sexual dimorphism; sex-dependent; bone-dependent

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Black, A. (2020). Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/21267

Chicago Manual of Style (16^th Edition):

Black, Alicia. “Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes.” 2020. Masters Thesis, University of Guelph. Accessed January 17, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/21267.

MLA Handbook (7^th Edition):

Black, Alicia. “Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes.” 2020. Web. 17 Jan 2021.

Vancouver:

Black A. Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes. [Internet] [Masters thesis]. University of Guelph; 2020. [cited 2021 Jan 17]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/21267.

Council of Science Editors:

Black A. Integrin alpha 1 beta 1 has limited influence on epidermal growth factor receptor signaling but sex-dependent effects on estrogen receptor beta in murine knee chondrocytes. [Masters Thesis]. University of Guelph; 2020. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/21267

University of Western Ontario

16. Hijazi, Ayten. Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development.

Degree: 2016, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/3845

► Prenatal exposure to bisphenol A (BPA), one of the most prevalent endocrine disrupting chemicals, is associated with lung dysfunction and diseases in later life. However,… (more)

▼ Prenatal exposure to bisphenol A (BPA), one of the most prevalent endocrine disrupting chemicals, is associated with lung dysfunction and diseases in later life. However, it is unknown if this association has a fetal origin. In this thesis, a series of in vivo and in vitro experiments were conducted to determine the effects of prenatal exposure to BPA on fetal lung development, and define the underlying molecular mechanisms. Environmentally relevant doses of BPA were administered to pregnant mice via diet from embryonic day (E) 7.5 to 18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of key molecular markers of lung maturation. My main findings were: (a) BPA severely retards fetal lung maturation as evidenced by diminished alveolar airspace and thickened septa, hallmarks of lung immaturity; (b) this immaturity is characterized by aberrant alveolar epithelial type I cell differentiation; and (c) the effects of BPA are likely mediated through the glucocorticoid signaling pathway, because the expression of epithelial sodium channel g (ENaCγ), a well-known glucocorticoid receptor (GR) target gene, is down-regulated in BPA-exposed fetal lungs. Moreover, maternal administration of dexamethasone rescues the lung immaturity phenotype. However, the precise molecular mechanisms by which BPA represses ENaCγ in lung cells were unknown. This important question was addressed using the A549 human lung epithelial cell line as an in vitro model system. I found that that (d) both dexamethasone and siRNA-mediated knockdown of GR expression blocked the inhibitory effects of BPA on ENaCγ expression, indicating that BPA suppresses ENaCγ via inhibition of GR activity. Given that BPA is known to function as a pro-inflammatory factor via the estrogen receptor b (ER b), and a mutual antagonism exists between the pro-inflammatory transcriptional factor NF-κB and GR, I then explored and provide evidence supporting the notion that (e) BPA acts on ER-β to activate the NF-κB signaling pathway, which in turn leads to diminished GR activity and consequent repression of ENaCγ expression in lung cells. Taken together, these findings demonstrate that prenatal exposure to BPA disrupts fetal lung maturation, and suggest a fetal origin for BPA-induced lung dysfunction and diseases.

Subjects/Keywords: Endocrine-Disrupting Chemical; Bisphenol A; Fetal Exposure; Fetal Development; Lung Maturation; Reduced Lung Function; Lung Disease; Glucocorticoid Signaling Pathway; NF-κB signaling pathway; Estrogen Receptor-β signaling pathway; Circulatory and Respiratory Physiology; Disorders of Environmental Origin; Other Chemicals and Drugs; Respiratory Tract Diseases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hijazi, A. (2016). Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3845

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hijazi, Ayten. “Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development.” 2016. Thesis, University of Western Ontario. Accessed January 17, 2021. https://ir.lib.uwo.ca/etd/3845.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hijazi, Ayten. “Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development.” 2016. Web. 17 Jan 2021.

Vancouver:

Hijazi A. Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development. [Internet] [Thesis]. University of Western Ontario; 2016. [cited 2021 Jan 17]. Available from: https://ir.lib.uwo.ca/etd/3845.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hijazi A. Effects of Prenatal Exposure to Bisphenol A on Fetal Lung Development. [Thesis]. University of Western Ontario; 2016. Available from: https://ir.lib.uwo.ca/etd/3845

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

17. Poulard, Coralie. Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2013, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2013LYO10142

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Le cancer du sein représente une cause de mortalité élevée chez la femme. Le cancer du sein est un cancer hormono-dépendant. De ce fait, il… (more)

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Le cancer du sein représente une cause de mortalité élevée chez la femme. Le cancer du sein est un cancer hormono-dépendant. De ce fait, il est extrêmement important de définir le rôle joué par les différents acteurs protéiques de la signalisation hormonale, notamment la signalisation œstrogénique. Parallèlement aux effets nucléaires de ERa où l'hormone lie le récepteur nucléaire et régule la transcription génique, il existe une voie dite non génomique. L'équipe a montré que les œstrogènes induisent la méthylation de ERa, qui est un prérequis au recrutement de la Pl3K et de la tyrosine kinase Src, conduisant à l'activation de molécules de signalisation telles que les MAPK et Akt, induisant prolifération et survie cellulaire. Durant ma thèse, j'ai pu démontrer que le complexe mERa/Src/Pl3K existe in vivo et constitue un nouveau biomarqueur indépendant de mauvais pronostique. La recherche de nouveaux partenaires du complexe mERa/Src/Pl3K nous a permis d'identifier le suppresseur de tumeur LKB1 et l'arginine déméthylase JMJD6. De façon surprenante, l'étude de l'expression de LKB1 par immunohistochimie dans une cohorte de tumeurs mammaires a montré une dualité fonctionnelle selon sa localisation subcellulaire. De plus, nous avons démontré que JMJD6 s'associe à ERa méthylé lorsque le récepteur est complexé à Src et Pl3K, et permet ainsi la déméthylation de ERa et la dissociation du complexe mERa/Src/Pl3K. Ce travail a ainsi pu mettre en évidence que les différents acteurs de cette signalisation peuvent constituer des éléments clés au diagnostique mais également lors de la décision thérapeutique, puisque qu'il existe des drogues peuvant cibler cette voie de signalisation

Estrogen receptor a {ERa}, belonging to the superfamily of hormone nuclear receptors, regulates many physiological processes, notably the growth and survival of breast tumor cells, acting as a ligand-dependent transcription factor. Besides to the well described transcriptional effects, estrogen also mediate extranuclear events called non genomic signaling via its receptor. /n fact, team shows that ERa is methylated and that this event is a prerequisite for the recrutement of Src and P/3K and the activation of Akt which orchestrate cell proliferation and survival. During my PhD, / demonstrated that the non genomic signaling complex mERa/Src/P/3K exists in vivo and is operative. /n addition, the complex is found to be an independent prognostic factor for disease free survival. This is an emergent concept that estrogen non genomic pathway is operative in vivo and can constitute a new therapeutic targets. The search for new partners of the complex has allowed us to identify the tumor suppressor LKB1 and arginine demethylase JMJD6. Expression of LKB1 in immunohistochemistry revealed dual properties based on its subcellular localization. When LKB1 is complexed with mERa/Src/P/3K it may acquire oncogenic properties. /n addition, JMJD6 interacts with methylated ERa when the receptor is associated with Src and P/3K, and allows the demethylation of ERa and the…

Advisors/Committee Members: Le Romancer, Muriel (thesis director).

Subjects/Keywords: Récepteur aux oestrogènes; Voies non génomiques; Méthylation des arginines; PRMT1; Déméthylation; LKB1; JMJD6; Cancer du sein; Estrogen receptor; Non genomic signaling; Arginine methylation; PRMT1; Demethylation; LKB1; JMJD6; Breast cancer; 616.99

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Poulard, C. (2013). Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2013LYO10142

Chicago Manual of Style (16^th Edition):

Poulard, Coralie. “Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer.” 2013. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 17, 2021. http://www.theses.fr/2013LYO10142.

MLA Handbook (7^th Edition):

Poulard, Coralie. “Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer.” 2013. Web. 17 Jan 2021.

Vancouver:

Poulard C. Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2013. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2013LYO10142.

Council of Science Editors:

Poulard C. Étude de la régulation de la méthylation du récepteur aux œstrogènes de type alpha dans le cancer du sein : Regulation of estrogen receptor alpha methylation in breast cancer. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2013. Available from: http://www.theses.fr/2013LYO10142

18. Omarjee, Soleilmane. Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer.

Degree: Docteur es, Biologie, 2016, Lyon

URL: http://www.theses.fr/2016LYSE1041

►

Nous avons étudié un nouveau varant d'épissage de ERa, nommé ERa36 et son implication dans la signalisation non génomique des œstrogènes. Contrairement à ERa, ce… (more)

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Nous avons étudié un nouveau varant d'épissage de ERa, nommé ERa36 et son implication dans la signalisation non génomique des œstrogènes. Contrairement à ERa, ce variant a une localisation majoritairement cytoplasmique et membranaire. Il possède une partie C-Terminale unique due à l'épissage alternatif. Nous avons découvert que le domaine C-Termonal de ERa36 contient un D-Domain, qui lui confère la capacité de se lier directement avec des protéines de la famille MAPK. En utilisant des approches in-vitro et in-cellulo, nous avons démontré que ERa36 se lie spécifiquement à la kinase ERK2 en réponse d'une stimulation ostrogénique ou anti-ostrogénique. Nous avons démontré que ERK2 lié à ERa36 lui conférait une résistance à la déphosphorylation par la phosphatase MKP3, conduisant ainsi à une activation soutenue de la voir ERK. Ce mécanisme a des effets profonds sur les cibles de ERK. En effet, l'inhibition pharmacologique de l'interaction ERa36/ERK2 diminue la phosphorylation de la Paxilline, qui a son tour conduit à une répression de la Cycline D1. En plus de ces observations, nous avons démontré, en étudiant l'expression de ERa36 par IHC dans 175 tumeurs de sein, que son expression était un facteur prédictif de métastases à distance et conduit à une diminution de la survie globale. Ce travail pourrait amener à dire que l'expression de ERa36 constitue un nouveau biomarqueur dans le cancer du sein

We study a novel splice variant of ERa, named ERa36, and its involvement in estrogen non genomic signaling. Unlike ERa, this variant has main cytoplasmic/plasma membrane localization and alternative splicing confers it with a unique, previously unidentified C-terminal domain. Interestingly, we found that ERa36 C-terminal domain contains a putative MAPK binding D-Domain for the serine/threonine kinase ERK2. This domain is a docking site for members of the MAPK family. Coupling in-vitro and in-cellulo approaches, we demonstrated that ERa36 binds specifically to ERK2 following estrogen, as well as clinical anti-estrogen (tamoxifen) stimulation.We demonstrated that ERa36 binding to ERK2 inhibits the latter’s dephosphorylation by the dual phosphatase MKP3, thereby leading to a sustained ERK activation. This mechanism had profound effects on ERK’s downstream molecular targets. In fact, pharmacological inhibition of the ERa36/ERK2 interaction abrogated the phosphorylation of Paxillin, which in turn led to a downregulation of CyclinD1 transcription.Futhermore, IHC analysis of ERa36 expression in 175 patient breast tumors revealed that its expression constituted an independent predictor of distant metastasis and influenced on overall survival. In conclusion, ERa36 expression could constitute a new biomarker in breast cancer

Advisors/Committee Members: Le Romancer, Muriel (thesis director).

Subjects/Keywords: Œstrogènes; MAPK; Voie non-génomique; MKP3; ERa36; Cancer du Sein; Cycline D1; Estrogen; MAPK; Non genomic signaling; MKP3; ERa36; Breast cancer; Cyclin D1; 571.7

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Omarjee, S. (2016). Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2016LYSE1041

Chicago Manual of Style (16^th Edition):

Omarjee, Soleilmane. “Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer.” 2016. Doctoral Dissertation, Lyon. Accessed January 17, 2021. http://www.theses.fr/2016LYSE1041.

MLA Handbook (7^th Edition):

Omarjee, Soleilmane. “Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer.” 2016. Web. 17 Jan 2021.

Vancouver:

Omarjee S. Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer. [Internet] [Doctoral dissertation]. Lyon; 2016. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2016LYSE1041.

Council of Science Editors:

Omarjee S. Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes : Study of the role of estrogen receptor variant, ERa36, in non genomic signaling and breast cancer. [Doctoral Dissertation]. Lyon; 2016. Available from: http://www.theses.fr/2016LYSE1041

Universidade do Rio Grande do Sul

19. Seibel, Fernanda Eugênia Rodrigues. Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata.

Degree: 2014, Universidade do Rio Grande do Sul

URL: http://hdl.handle.net/10183/114574

►

Em homens, com o avanço da idade ocorre declínio dos níveis plasmáticos de androgênios, enquanto os níveis de estrogênio permanecem constantes ou aumentados. Isto leva… (more)

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Em homens, com o avanço da idade ocorre declínio dos níveis plasmáticos de androgênios, enquanto os níveis de estrogênio permanecem constantes ou aumentados. Isto leva à diminuição da razão androgênio/estrogênio, sugerindo que os estrogênios podem ter um papel no desenvolvimento do câncer de próstata. Os estrogênios estão relacionados à indução da proliferação celular através da sua ligação aos receptores clássicos (ERs) e ao receptor não clássico GPER. Ambos receptores podem ativar as vias de sinalização PI3K e MAPK relacionadas à sobrevivência celular e ter importância no desenvolvimento do câncer de próstata (CaP) e da hiperplasia prostática benigna (HPB). Objetivo: Avaliar a relação dos receptores de estrogênio GPER, ERα, ERβ e suas isoformas com as vias PI3K e MAPK pela análise da expressão gênica e proteica dos receptores de estrogênio ERα, ERβ e GPER, pela análise da expressão de proteínas da via MAPK e PI3K e do estrogênio tecidual nos grupos HPB e CaP. Métodos: Tecidos prostáticos provenientes de CaP e de HPB foram submetidos à extração de RNA, o RNA foi reversamente transcrito para cDNA e avaliado usando q-PCR para a expressão dos receptores de estrogênio GPER, ERα, ERβ e suas isformas. A expressão proteica de GPER, ERα, ERβ, mTOR, PI3K e c-JUN e a ativação da p38α, ERK1/2, JNK, AKT e GSK3β foram analisadas por Western blot. A técnica de imunofluorescência foi utilizada para verificação da colocalização dos receptores GPER e ERα em estroma e epitélio de HPB e CaP. Resultados: Comparações entre os tecidos hiperplásico e de carcinoma indicaram uma maior expressão gênica e proteica de ERα e GPER em amostras de CaP comparadas à HPB. Além disso, a ativação da AKT, GSK3β e JNK e a expressão proteica da PI3K e c-JUN foram significativamente aumentadas nos tecidos de CaP enquanto que a expressão proteica de mTOR e a ativação de p38α e ERK estão diminuídas neste grupo. A expressão gênica do ERβ está aumentada no CaP porém não há diferença na expressão proteica entre os grupos. A análise da expressão gênica das isoformas do ERβ mostrou diminuição de ERβ1 e ERβ6 e aumento das isoformas ERβ2 e ERβ5 no CaP. Não foram detectadas as expressões das isoformas ERβ3 e ERβ4 em ambos os grupos. Nossos resultados também mostraram que os receptores GPER e ERα estão colocalizados no núcleo de células estromais de HPB e CaP. Além disso, o GPER está expresso com maior intensidade no epitélio de ambos os grupos enquanto o ERα está expresso com maior intensidade no estroma do CaP. A medida do estrogênio tecidual mostrou aumento deste no tecido de CaP em relação ao de HPB. Conclusões: O presente estudo mostrou aumento do estrogênio e de seus receptores ERα e GPER no CaP em relação ao HPB indicando que há modulação estrogênica na próstata. Além disso, proteínas das vias MAPK e PI3K que podem ser moduladas pela ação estrogênica estão expressas de maneiras diferentes em ambos os grupos. O estudo da ação estrogênica parece ser importante para o entendimento da progressão das doenças prostáticas.

In men with advancing age decline in…

Advisors/Committee Members: Brum, Ilma Simoni.

Subjects/Keywords: Receptor alfa de estrogênio; Estrogen receptors; Receptor beta de estrogênio; Signaling pathways; MAPK; Transdução de sinal; Proteína quinase 1 ativada por mitógeno; PI3K; Prostate; Neoplasias da próstata; Hiperplasia prostática

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Seibel, F. E. R. (2014). Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/114574

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Seibel, Fernanda Eugênia Rodrigues. “Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata.” 2014. Thesis, Universidade do Rio Grande do Sul. Accessed January 17, 2021. http://hdl.handle.net/10183/114574.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Seibel, Fernanda Eugênia Rodrigues. “Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata.” 2014. Web. 17 Jan 2021.

Vancouver:

Seibel FER. Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10183/114574.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Seibel FER. Receptores de estrogênio e vias de sinalização MAPK e P13K em hiperplasia prostática benigna e câncer de próstata. [Thesis]. Universidade do Rio Grande do Sul; 2014. Available from: http://hdl.handle.net/10183/114574

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

20. Laliotis, Aggelos. Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου.

Degree: 2015, University of Crete (UOC); Πανεπιστήμιο Κρήτης

URL: http://hdl.handle.net/10442/hedi/35984

► Data from laboratory and clinical studies have shown the presence of intracellular pathways such as Ras / Raf-1 / ERK1 / 2, in breast cancer.… (more)

▼ Data from laboratory and clinical studies have shown the presence of intracellular pathways such as Ras / Raf-1 / ERK1 / 2, in breast cancer. However, the interactions between these intracellular pathways and specific cellular receptors as well as the relation of these pathways with molecules associated with tumor cell proliferation are not fully understood.The main purpose of this study was to clarify the correlations that exist between cellular receptor molecules, intracellular signaling pathways and their target molecules like pElk-1 and others such as Cyclin D1 and Ki-67 that play an important role in the transition of cells from the G1 to the S phase. Further objective of this study was to investigate the relationship between these molecules with breast tumors’ pathological characteristics, their proliferative activity, their ability to metastasize and finally with patients'survival.One hundred and seventy (n = 170) of female operable breast cancer cases were studied for the expression of the ERa, ERb, PR, Her-2, receptor and the expression of intracellular molecules ERK1 / 2, pElk-1, CyclinD1 and Ki6 using immunohistochemistry 7.This study was the first to demonstrate increased expression of the phosphorylated form of the protein Elk-1 (pElk-1) in tissue samples from human breast cancer using immunohistochemistry. We fουnd a statistically significanτ relationship between the expression of estrogen receptors ERa with pElk-1 and Cyclin D1 and between pElk-1 and Cyclin D1, as well. There was also a statistically significant correlation between the expression of ERK1 / 2 and pELk-1, but we did not find any other relationship between ERK1 / 2 and the other molecules. We have also found a positive correlation between the expression of ER and PR and a negative relation of their expression with HER-2. The mean overall survival was increased among patients with positive tumors for p Elk-1 and ERK1/2 although not statistically significant.The expression of pElk-1 and Cyclin D1 in Basal cell carcinomas was reduced. We have noticed an increase of the expression of Cyclin D1 in Luminal B HER-2 negative breast carcinomas. Although not statistically significant, there was increased expression of pElk-1 in Luminal A and Luminal B HER-2 negative breast carcinomas. The median value for the pElk-1 was significantly higher compared to its expression in Basal and HER-2 tumors. It is also important to stress that H-score for pElk-1 was higher in Luminal A and Luminal B / Her-2 negative tumors compared to the Luminal B / Her-2 positive, HER-2 and Basal cell carcinomas.Our findings offer a new perspective for the role of ERK1/2 and pElk-1 in breast neoplasia suggesting a direct relation for pElk-1 molecule to tumor biology and a putative target of personalized breast cancer therapies, although its prognostic/discriminant role is not supported.Further studies of ER, PR, HER-2 expression in relation to the Raf-1 / MEK-1 / ERK1 / 2 pathway as well as to the p Elk-1, CyclinD1 and Ki-67 expression in combination with other intracellular…

Subjects/Keywords: Καρκίνος μαστού; Κυτταρικός πολλαπλασιασμός; Στάδιο νόσου; Elk-1; Ras/Raf/MAPK signaling pathway; HER-2/neu; Cyclin D1; Estrogen and progesterone hormone receptors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Laliotis, A. (2015). Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου. (Thesis). University of Crete (UOC); Πανεπιστήμιο Κρήτης. Retrieved from http://hdl.handle.net/10442/hedi/35984

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Laliotis, Aggelos. “Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου.” 2015. Thesis, University of Crete (UOC); Πανεπιστήμιο Κρήτης. Accessed January 17, 2021. http://hdl.handle.net/10442/hedi/35984.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Laliotis, Aggelos. “Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου.” 2015. Web. 17 Jan 2021.

Vancouver:

Laliotis A. Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου. [Internet] [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10442/hedi/35984.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Laliotis A. Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού: σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου. [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2015. Available from: http://hdl.handle.net/10442/hedi/35984

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Jung, Min-Yong 1989-. HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers.

Degree: 2016, University of Saskatchewan

URL: http://hdl.handle.net/10388/7660

► The human ether-a-go-go-related gene (HERG) potassium channel, a known regulator of cell proliferation, is overexpressed in several cancer cell lines. Despite its importance, there have… (more)

▼ The human ether-a-go-go-related gene (HERG) potassium channel, a known regulator of cell proliferation, is overexpressed in several cancer cell lines. Despite its importance, there have not been many studies regarding the mechanism by which it contributes to aberrant proliferation of cancer cells. In this study, we identified a novel estrogen signalling pathway that plays a role in regulating cell proliferation in estrogen receptor positive breast cancer cells. We provide the initial characterization of this signal transduction pathway which results in up-regulation of HERG channels and increased proliferation of estrogen receptor positive breast cancer cell lines. Using biochemical and confocal microscopy imaging, we revealed that there is a protein-protein interaction between HERG and Signal Transducers and Activators of Transcription 1 (STAT1) in breast cancer cell lines that express estrogen receptors (ER+) (MCF-7, T47D) and in those that lack ERs (ER-) (MDA-MB-231, BT-20). After estrogen treatment (E2, 10µM), only the ER+ human breast cancer cell lines showed increased co-precipitation of HERG and STAT1 and higher levels of subcellular colocalization, and these effects were prevented by pharmacological blockers of ERs (ICI 182 780, 5nM) or STAT1 (fludarabine, 50µM). Furthermore, we demonstrated that the enhanced STAT1 and HERG interaction induced by estrogen is important for upregulation of the HERG channel surface expression. Consistent with our prediction that HERG surface expression plays a critical role in cancer cell proliferation, proliferation assays revealed a marked upregulation of ER+ cancer cell proliferation after E2 stimulation, and this was prevented by ICI, fludarabine and the HERG blocker E4031 (10µM). Together, these results suggest that there is an estrogen receptor mediated signalling pathway involving a physical complex between STAT1 and HERG channels, and this proposed pathway may be an attractive strategy for anti-cancer therapeutic targeting of ER+ human breast tumors. Next, since it is known that HERG contains multiple tyrosine residues whose phosphorylation could be increased after estrogen receptor stimulation, we hypothesized that these phosphorylated tyrosine residues could serve as binding sites of the SH2 domain of STAT1. We have used FR-peptide, a 28 amino acid peptide mimetic of STAT1 SH2 domain, to disrupt interaction between HERG and STAT1. Our biochemistry and imaging data demonstrated that FR-peptide did disrupt the HERG-STAT1 interaction, and this cell-permeable peptide did prevent the estrogen-induced upregulation of HERG channel and cancer cell proliferation of ER+ breast cancer cells. Finally, we also demonstrated that the HERG-STAT1 interaction was specific to breast cancer cells, as similar biochemical studies failed to show physical interactions in normal brain and cardiac tissue. Together, this study reveals a novel estrogen receptor signalling pathway which enhances the HERG channel surface expression and its contribution to cancer cell proliferation in ER+… Advisors/Committee Members: Cayabyab, Francisco, Campanucci, Veronica, Taghibiglou, Changiz, Fisher, Thomas, Vizeacoumar, Franco.

Subjects/Keywords: HERG; STAT1; Estrogen; Estrogen Receptor; Breast Cancer; Cell Proliferation; Signaling Pathway

…of STAT1. 13 Figure 1.3 Proposed model for estrogen induced overexpression of HERG… …channels in estrogen receptor-positive human breast cancer cell lines. 15 Figure 3.1 Breast… …x29; cell lines. 25 Figure 3.3 Confocal images showing the effect of estrogen on HERG and… …of HERG potassium channels after estrogen Treatment 29 Figure 3.5.1 Cell proliferation… …assay and block of estrogen-induced proliferation by HERG channel blocker (E4031) in…

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jung, M. 1. (2016). HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/7660

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jung, Min-Yong 1989-. “HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers.” 2016. Thesis, University of Saskatchewan. Accessed January 17, 2021. http://hdl.handle.net/10388/7660.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jung, Min-Yong 1989-. “HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers.” 2016. Web. 17 Jan 2021.

Vancouver:

Jung M1. HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers. [Internet] [Thesis]. University of Saskatchewan; 2016. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10388/7660.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jung M1. HERG and STAT1 Interactions in Estrogen Receptor Positive and Estrogen Receptor Negative Human Breast Cancers. [Thesis]. University of Saskatchewan; 2016. Available from: http://hdl.handle.net/10388/7660

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

22. Piperigkou, Zoi. Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού.

Degree: 2018, University of Patras; Πανεπιστήμιο Πατρών

URL: http://hdl.handle.net/10442/hedi/43995

► Estrogen receptors (ERs) have pivotal roles in breast cancer growth and progression. Even though the contribution of ERα in the modulation of breast cancer cells'… (more)

▼ Estrogen receptors (ERs) have pivotal roles in breast cancer growth and progression. Even though the contribution of ERα in the modulation of breast cancer cells' behavior is thoroughly studied, the biological functions of its isoform, ERβ, are less elucidated. In the present doctoral thesis, we demonstrated that ERβ suppression in the highly aggressive, ERβ-positive MDA-MB-231 breast cancer cells (shERβ MDA-MB-231) resulted in profound phenotypic changes, inhibition of EMT process and major changes in the properties as well as in gene and protein expression levels of certain functional matrix components of breast cancer cells in a 17-β-estradiol (E2)-independent manner. As observed by scanning electron microscopy, ERβ suppression strongly affects the morphology of shERβ MDA-MB-231 cells, which is followed by downregulated expression levels of the mesenchymal markers fibronectin and vimentin, whereas it increases the expression levels of epithelial marker E-cadherin and cell-cell junctions. These alterations are followed by reduced levels of cell functional properties that promote the aggressiveness of these cells, such as proliferation, migration, spreading capacity, invasion and adhesion. Notably, ERβ suppression reduces the migration of MDA-MB-231 breast cancer cells via EGFR/IGF-IR and JAK/STAT signaling pathways. Moreover, our findings revealed that ERβ has a crucial role in modulation of mRNA levels and protein expression of several matrix mediators, including the transmembrane syndecans and intracellular serglycin, several MMPs, plasminogen activation system components and receptor tyrosine kinases. These data clearly demonstrate that ERβ plays a crucial role in mediating cell behavior and ECM composition of the highly aggressive MDA-MB-231 cells and it opens a new area of research to further understand its role and to improve pharmaceutical targeting of the non-hormone-dependent breast cancer.The epigenetic alterations are responsible for the ability of the tumor cells to metastasize. In the present study, we demonstrated that ER status is associated with distinct miRNA expression profiles in MCF-7 and MDA-MB-231 breast cancer cells, and that mainly miR-10b (oncogenic miRNA) and miR-200b (EMT inhibitor) are the key regulators of MDA-MB-231 cell behavior. Notably, the expression profiles of these miRNAs are mediated through EGFR/IGF-IR crosstalk with E2. Moreover, growing ERα-positive, MCF-7, and ERβ-positive, MDA-MB-231, cells in estrogen-free medium resulted in a diverse impact on miRNA expression and the behavior of these cells, suggesting the specific effect of E2 on the miRNAs expression profile, depending on the ER status of breast cancer cells. Specifically, ERβ suppression in MDA-MB-231 breast cancer cells results in significant changes in the expression profiles of specific miRNAs that regulate breast cancer progression, including miR-10b, miR-200b and miR-145 (tumor-suppressive miRNA). Enhanced miR-10b expression or miR-145 silencing in shERβ MDA-MB-231 cells revealed that these miRNAs can regulate…

Subjects/Keywords: Καρκίνος μαστού; Οιστρογονοϋποδοχείς; Οιστρογονοϋποδοχέας β; MicroRNAs; Mετασχηματισμός από επιθηλιακό σε μεσεγχυματικό φαινότυπο; Εξωκυττάριος χώρος; Κυτταρική σηματοδότηση; Μεταλλοπρωτεϊνάσες; Πρωτεογλυκάνες; Breast cancer; Estrogen receptors; Estrogen receptor beta; MicroRNAs; Epithelial-to-mesenchymal-transition; Extracellular matrix; Cellular signaling; Matrix metalloproteinases; Proteoglycans

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Piperigkou, Z. (2018). Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/43995

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Piperigkou, Zoi. “Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού.” 2018. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed January 17, 2021. http://hdl.handle.net/10442/hedi/43995.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Piperigkou, Zoi. “Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού.” 2018. Web. 17 Jan 2021.

Vancouver:

Piperigkou Z. Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2018. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10442/hedi/43995.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Piperigkou Z. Μελέτη ρυθμιστικών μηχανισμών έκφρασης βιομορίων, λειτουργικών ιδιοτήτων και μορφολογικών χαρακτηριστικών των καρκινικών κυττάρων μαστού. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2018. Available from: http://hdl.handle.net/10442/hedi/43995

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cincinnati

23. LE, HOA HIEN. Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells.

Degree: PhD, Medicine : Molecular, Cellular and Biochemical Pharmacology, 2008, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218807307

► Estrogens influence the normal function and development of the mammalian nervous system. 17β-Estradiol (E₂) mediates many of its effects through modulation of gene transcription via… (more)

Subjects/Keywords: Pharmacology; estradiol; estrogen; estrogen receptor; endocrine disrupting chemicals; cerebellum; granule cells; viability; rapid actions; intracellular signaling pathways

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

LE, H. H. (2008). Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218807307

Chicago Manual of Style (16^th Edition):

LE, HOA HIEN. “Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells.” 2008. Doctoral Dissertation, University of Cincinnati. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218807307.

MLA Handbook (7^th Edition):

LE, HOA HIEN. “Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells.” 2008. Web. 17 Jan 2021.

Vancouver:

LE HH. Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells. [Internet] [Doctoral dissertation]. University of Cincinnati; 2008. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218807307.

Council of Science Editors:

LE HH. Definition of Rapid 17β-Estradiol Signaling Networks in Developing Cerebellar Granule Cells. [Doctoral Dissertation]. University of Cincinnati; 2008. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1218807307

University of Illinois – Urbana-Champaign

24. Bhatt, Shweta. Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells.

Degree: PhD, 0318, 2010, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/17032

► Breast cancer is one of the most highly diagnosed cancers in women and the second largest cause of death of women in United States. The… (more)

▼ Breast cancer is one of the most highly diagnosed cancers in women and the second largest cause of death of women in United States. The anti-estrogen tamoxifen which blocks gene expression through estradiol bound ER??, and hence the growth stimulatory effects of estradiol, has been widely used for decades for treating patients with ER?? positive or hormone dependent breast cancer. Despite its obvious benefits, in as high as 40% of the patients receiving tamoxifen therapy there is an eventual relapse of the disease largely due to acquired resistance to the drug, underlying mechanism for which is rather poorly understood. Elucidating the molecular basis underlying ???acquired tamoxifen resistance??? and agonistic effects of tamoxifen on cellular growth was the primary focus of my doctoral research. We addressed this by two approaches, one being studying the molecular mechanism for the regulation of cellular levels of ER?? so as to prevent its loss in ER?? positive or restore its levels in ER?? negative breast cancers and second to investigate the role of tamoxifen in modulating the expression of ER?? target genes independent of estradiol as a function of its stimulatory or estrogenic effects on breast cancer cell growth. To this end we found a novel mechanism involving the E-3 ubiquitin ligase and major regulator of cell cycle progression, Skp2, in the proteasomal degradation of ER?? upon activation by p38MAPK. Interestingly, this regulation of ER?? by sequential actions of p38MAPK and Skp2 that was observed specifically during the G1/S transition and S-phases of the cells cycle was found to be critical for the progression of cells through S-phase. The underlying mechanism of increased cell cycle entry due to concerted actions of ER?? and Skp2 was later identified to be due to positive regulation of the trans-activation function of ER?? by Skp2, most likely due to efficient cycling of the receptor on target gene promoter upon Skp2 driven turnover. The impact of Skp2 on ER?? mediated growth of tamoxifen resistant breast cancer cells was far more pronounced in the presence of tamoxifen than estradiol. In order to find the likely mechanism driving Skp2 mediated growth through ER??, in the presence of tamoxifen, we attempted to identify co-regulators unique to tamoxifen bound ER?? and identified Oct-3/4, a transcription factor with well-known role in embryonic stem cell growth and differentiation, to be a specific regulator of tamoxifen, not estradiol, mediated gene regulation through ER??. Our work highlights a novel mechanism for the induction of Oct-3/4 in response to tamoxifen, not estradiol, largely due to p38MAPK initiated and Skp2 mediated degradation of Nkx3-1, a co-repressor of Oct-3/4 expression through ER??. Interestingly, further investigation revealed Oct-3/4 transcription factor binding sites were enriched in genes that recruited ER?? preferentially or exclusively in the presence of tamoxifen (by >5 fold compared to estradiol). Oct-3/4 induction by tamoxifen appeared to be followed by recruitment… Advisors/Committee Members: Katzenellenbogen, Benita S. (advisor), Katzenellenbogen, Benita S. (Committee Chair), Shapiro, David J. (committee member), Bagchi, Milan K. (committee member), Hergenrother, Paul J. (committee member).

Subjects/Keywords: Estrogen Receptor signaling; Breast Cancer; Skp2 mediated Ubiquitination; p38MAPK signaling; Cell cycle regulation in Breast cancer cells.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bhatt, S. (2010). Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/17032

Chicago Manual of Style (16^th Edition):

Bhatt, Shweta. “Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells.” 2010. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 17, 2021. http://hdl.handle.net/2142/17032.

MLA Handbook (7^th Edition):

Bhatt, Shweta. “Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells.” 2010. Web. 17 Jan 2021.

Vancouver:

Bhatt S. Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2010. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2142/17032.

Council of Science Editors:

Bhatt S. Cross-modulatory Actions of Cell Cycle Machinery on Estrogen Receptor-alpha Level and Transcriptional Activity in Breast Cancer Cells. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2010. Available from: http://hdl.handle.net/2142/17032

25. Bouris, Panagiotis. Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού.

Degree: 2017, University of Patras; Πανεπιστήμιο Πατρών

URL: http://hdl.handle.net/10442/hedi/41457

►

The aggressive behavior and the mesenchymal phenotype are two critical cancer cell properties which are closely associated with tumor development, progression and metastasis. The regulation… (more)

▼

The aggressive behavior and the mesenchymal phenotype are two critical cancer cell properties which are closely associated with tumor development, progression and metastasis. The regulation of these properties in breast cancer is significantly mediated by several signaling molecules, including estrogen receptors and receptors tyrosine kinases. Some ECM molecules, such as proteoglycans and proteolytic enzymes, are also crucial mediators of the above mentioned cellular properties in cancer. Our findings revealed specific molecules and possible mechanisms of action which actively mediate the regulation of aggressiveness and the mesenchymal morphology of breast cancer cells. More specifically, we demonstrated that the silencing of ERα induces EMT and promotes the aggressive behavior of MCF-7 breast cancer cells. In addition, the suppression of ERα activates cell signaling which is responsible for the mediation of aggressiveness, as well as enhances the expression and the activity of a plethora of critical proteolytic molecules. On the other hand, we demonstrated that IGF-IR promotes the mild behavior of breast cancer cells through an ERα-dependent manner, and the same time regulates the expression of specific MMPs/TIMPs. Furthermore, we report that the inhibition of the RTKs AXL and PDGFRβ causes a partial MET and strongly suppresses the high aggressive behavior of MDA-ΜΒ-231 breast cancer cells, thus highlighting the crucial role of these RTKs on the maintenance of mesenchymal phenotype and the aggressiveness in breast cancer. Moreover, the impact of AXL and PDGFRβ on cell signaling, while the crosstalk between the pathways of the RTKs with TGFβ signaling axis was also revealed. Finally, we demonstrated that serglycin mediates the induction of aggressiveness in breast cancer, through the regulation of crucial signaling pathways, including the IL-8/CXCR-2 pathway. Last but not least, it was shown that the overexpression of serglycin enhances the biosynthesis and the activity of the proteolytic network molecules, while it partly induces EMT and confers chemoresistance against commercially available anticancer drugs. Collectively, our data define the decisive regulatory role of all the above mentioned effectors of the aggressive behavior and the mesenchymal phenotype of breast cancer cells, as well as reveal possible mechanisms of action, thus highlighting the complexity for the regulation of these cell properties in breast cancer.

Η επιθετική συμπεριφορά και ο μεσεγχυματικός φαινότυπος είναι δυο ιδιότητες των καρκινικών κύτταρων οι οποίες σχετίζονται άμεσα με την ανάπτυξη, την εξέλιξη και τη μετάσταση του όγκου. Στον καρκίνο του μαστού η ρύθμιση αυτών των ιδιοτήτων φαίνεται να διαμεσολαβείται καθοριστικά από διάφορους σηματοδοτικούς άξονες, όπως οι οιστρογονοϋποδοχείς και συγκεκριμένοι υποδοχείς κινασών τυροσίνης. Τα μόρια του ECM, συμπεριλαμβανομένων των πρωτεογλυκανών και των πρωτεολυτικών ενζύμων, είναι επίσης σημαντικοί τελεστές της επαγωγής αυτών των δυο ιδιοτήτων στον καρκίνο. Τα αποτελέσματα της παρούσας μελέτης…

Subjects/Keywords: Καρκίνος του μαστού; Οιστρογονοϋποδοχέας α; Υποδοχείς κινασών τυροσίνης; Κυτταρική σηματοδότηση; Εξωκυττάριος χώρος; Μεταλλοπρωτεϊνάσες; Σεργλυκίνη; Ιντερλευκίνη-8; Breast cancer; Estrogen Receptor α; Receptor tyrosine kinases; Cell signaling; Extracellular matrix; Matrix metalloproteinases; Serglycin; Interleukin-8

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bouris, P. (2017). Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/41457

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bouris, Panagiotis. “Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού.” 2017. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed January 17, 2021. http://hdl.handle.net/10442/hedi/41457.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bouris, Panagiotis. “Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού.” 2017. Web. 17 Jan 2021.

Vancouver:

Bouris P. Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10442/hedi/41457.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bouris P. Δυναμική αλληλεπίδραση μεταξύ της σηματοδότησης του ERa, των αυξητικών παραγόντων και των μορίων του εξωκυττάριου χώρου στην επθετική συμπεριφορά των καρκινικών κυττάρων μαστού. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2017. Available from: http://hdl.handle.net/10442/hedi/41457

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

26. Greathouse, Kristen L. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.

Degree: PhD, 2010, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

► Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental… (more)

▼ Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through estrogen (E2)/ xenoestrogen inducedrapid ER signaling, which modifies the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2) via activation of the PI3K/AKT pathway. We further hypothesized that there is a xenostrogen-specific effect on this pathway altering patterns of histone modification, DNA methylation and gene expression. In addition to our novel finding that E2/DES-induced phosphorylation of EZH2 by AKT reduces the levels of H3K27me3 in vitro and in vivo, this work demonstrates in vivo that a brief neonatal exposure to GEN, in contrast to BPA, activates the PI3K/AKT pathway to regulate EZH2 and decreases H3K27me3 levels in the neonatal uterus. Given that H3K27me3 is a repressive mark that has been shown to result in DNA methylation and gene silencing we investigated the methylation of developmentally reprogrammed genes. In support of this evidence, we show that neonatal DES exposure in comparison to VEH, leads to hypomethylation of the promoter of a developmentally reprogrammed gene, Gria2, that become hyper-responsive to estrogen in the adult myometrium indicating vi that DES exposure alter gene expression via chromatin remodeling and loss of DNA methylation. In the adult uterus, GEN and BPA exposure developmentally reprogrammed expression of estrogen-responsive genes in a manner opposite of one another, correlating with our previous data. Furthermore, the ability of GEN and BPA to developmental reprogram gene expression correlated with tumor incidence and multiplicity. These data show that xenoestrogens have unique effects on the activation of non-genomic signaling in the developing uterus that promotes epigenetic and genetic alterations, which are predictive of developmental reprogramming and correlate with their ability to modulate hormone-dependent tumor development. Advisors/Committee Members: Cheryl L. Walker, Ph.D., David Johnson, Ph.D., Stephen Hursting, Ph.D., M.P.H..

Subjects/Keywords: Xenoestrogens; developmental reprogramming; uterine leiomyoma; epigenetics; non-genomic signaling; estrogen receptor; Cancer Biology; Developmental Biology; Molecular Biology; Other Pharmacology, Toxicology and Environmental Health

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Greathouse, K. L. (2010). XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

Chicago Manual of Style (16^th Edition):

Greathouse, Kristen L. “XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.” 2010. Doctoral Dissertation, Texas Medical Center. Accessed January 17, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/51.

MLA Handbook (7^th Edition):

Greathouse, Kristen L. “XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT.” 2010. Web. 17 Jan 2021.

Vancouver:

Greathouse KL. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. [Internet] [Doctoral dissertation]. Texas Medical Center; 2010. [cited 2021 Jan 17]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/51.

Council of Science Editors:

Greathouse KL. XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT. [Doctoral Dissertation]. Texas Medical Center; 2010. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/51

University of Vienna

27. Berner, Carolin Sophie. Modulation of epigenetic control of estrogen receptor α.

Degree: 2009, University of Vienna

URL: http://othes.univie.ac.at/7850/

► Epigenetik, die sich mit vererbbaren Zelleingenschaften befasst, welche die Genexpression beeinflussen ohne jedoch die DNA-Sequenz zu ändern, scheint auf grund ihres Ansprechens auf Umwelteinflüsse der… (more)

▼ Epigenetik, die sich mit vererbbaren Zelleingenschaften befasst, welche die Genexpression beeinflussen ohne jedoch die DNA-Sequenz zu ändern, scheint auf grund ihres Ansprechens auf Umwelteinflüsse der Mittler zwischen Umwelt und Genom eines Organismus zu sein. In Krebszellen sind die epigenetischen Muster im Vergleich zu gesunden Zellen stark verändert und haben Einfluß haben auf die Expression verschiedener Tumorsuppressorgene und Hormonrezeptoren, welche den Zellzyklus kontrollieren beziehungsweise auf Wachstumssignale reagieren. Zu den epigenetischen Mechanismen zählen die DNA Methylierung, Histon Modifikationen und der Einfluß kleiner, nicht kodierender RNAs. Besonders die DNA Methylierung wurde bis dato ausführlich erforscht, wobei man feststellte, dass eine umfassende DNA Hypomethylierung und genspezifische Hypermethylierung charakteristisch für alternde und neoplastische Zellen ist. Im Gegensatz zu den meisten genetischen Veränderungen, welche während der Karzinogenese auftreten, kann die DNA Methylierung durch den Einfluß präventiver oder therapeutischer Substanzen modifiziert werden. Zu diesen Substanzen zählen unter anderem bestimmte bioaktive Nahrungsinhaltsstoffe. Östrogenrezeptor alpha (ESR1) gehört zu der Superfamilie der nuklären Rezeptoren und ist durch seine Funktion als Liganden aktivierbarer Transkriptionsfaktor Mediator östrogener Einflüße auf die Zellen. In verschiedenen Krebsarten ist die Promoter Region von ESR1 hypermethyliert und dessen Expression somit fehlreguliert. Die Tumorsuppressorgene p16INK4a und p15INK4b sind Teil der Zellzyklus–Kontrolle. In Krebszellen sind diese genetisch verändert aber auch die promoter-methylierungsabhängige Inaktivierung von p16INK4a wurde in mehreren Krebsarten beobachtet, während selbiger Vorgang im p15INK4b Promoter vornehmlich in diversen Blutkrebsarten gefunden wurde. Um hormonelle und epigenetische Vorgänge ausgewählter bioaktiver Nahrungs-bestandteile zu verbinden, wurden Caco-2 Zellen mit mit Folsäure, Epigallocatechin-3-gallate (EGCG), Genistein, Butyrat, Resveratrol und Referenz DNA Methylierungs Inhibitor Zebularin behandelt und deren Einfluß auf den Promoter Methyleriungsstatus des Östrogenrezeptor alpha (ESR1) und der beiden Tumorsuppressorgene p16INK4a und p15INK4b bestimmt. Die Promotermethylierung wurde durch Bisulfit-Konversion und methylierungs-spezifischer nested PCR gemessen. Zusätzlich wurde mittels real-time PCR die Genexpression von ESR1 quantifiziert. Nach der Zellbehandlung mit Genistein, Folat, EGCG und Resveratrol konnte eine verstärkte ESR1 Promotermethylierung festgestellt werden, Zebularin und Butyrat verminderten diese. Die Genexpression korrelierte jedoch nur teilweise mit den Ergebnissen der Methylierung, was auf einen zuätzlichen epigenetischen Mechanismus wie Histonacetylierung in der Expressionsregulation von ESR1 schließen lässt. P15INK4b Promotermethylierung konnte duch Genistein und Folat verstärkt werden und zeigte sich durch Butyrat, EGCG, Resveratrol und Zebularine vermindert. Die stärkste Reaktion zeigte die…

Subjects/Keywords: 42.20 Genetik; 44.48 Medizinische Genetik; ESR1 / p15 / p16 / DNA Methylierung / Zebularin / Resveratrol / Butyrat / Genistein / EGCG / Folsäure / Epigenetik / Östrogen Signaltransduktion; ESR1 / p15 / p16 / DNA methylatio / zebularine / resveratrol / butyrate / genisteine / EGCG / folic acid / epigenetic / estrogen signaling

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Berner, C. S. (2009). Modulation of epigenetic control of estrogen receptor α. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/7850/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Berner, Carolin Sophie. “Modulation of epigenetic control of estrogen receptor α.” 2009. Thesis, University of Vienna. Accessed January 17, 2021. http://othes.univie.ac.at/7850/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Berner, Carolin Sophie. “Modulation of epigenetic control of estrogen receptor α.” 2009. Web. 17 Jan 2021.

Vancouver:

Berner CS. Modulation of epigenetic control of estrogen receptor α. [Internet] [Thesis]. University of Vienna; 2009. [cited 2021 Jan 17]. Available from: http://othes.univie.ac.at/7850/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Berner CS. Modulation of epigenetic control of estrogen receptor α. [Thesis]. University of Vienna; 2009. Available from: http://othes.univie.ac.at/7850/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

28. Durbin, Adam. Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma.

Degree: 2010, University of Toronto

URL: http://hdl.handle.net/1807/24739

►

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, with two predominant histologic subtypes: embryonal and alveolar. These histologies display distinct clinical courses, and… (more)

▼

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, with two predominant histologic subtypes: embryonal and alveolar. These histologies display distinct clinical courses, and despite refinements in dose and duration of multimodality therapy, the 5-year overall survival of patients diagnosed with metastatic RMS remains <30%. Thus, there is an urgent need to define novel targets for therapeutic intervention. Interrogation of cancer cell signal transduction pathways that regulate the pathogenic behaviours of tumor cells has been successful in defining targets in numerous tumor types. These have ultimately yielded clinically-relevant drugs that have improved the disease-free and overall survival of patients diagnosed with cancer. Work contained in this thesis describes the interrogation of several potential targets for inhibition in RMS. Interruption of RMS cell proliferation, survival and apoptosis is examined through disruption of the protein kinase integrin-linked kinase (ILK) and the nuclear receptor estrogen-receptor β. ILK, in particular, is demonstrated to have dual competing functions through the regulation of c-jun amino-terminal kinase (JNK) signaling: an oncogene in alveolar, and a tumor suppressor in embryonal RMS. These findings are recapitulated in other tumor cell lines, indicating that expression levels of JNK1 correlate with ILK function in a broad spectrum of tumor types. Furthermore, interruption of rhabdomyosarcoma cell migration as a surrogate marker of metastasis is examined through disruption of the stromal-cell derived factor 1α/chemokine (CXC)receptor 4 signaling network, as well as through cooperative interactions between ILK and the mammalian target of rapamycin. Finally, we demonstrate that the insulin-like growth factor pathway is a potential target for therapeutic inhibition, which also distinguishes tumors of embryonal and alveolar histology. These studies provide a rationale for the development of novel agents, as well as the use of established drugs targeting these pathways in rhabdomyosarcoma.

PhD

Advisors/Committee Members: Malkin, David, Medical Biophysics.

Subjects/Keywords: rhabdomyosarcoma; cell signaling; tumor suppressor; oncogene; metastasis; insulin-like growth factor; chemokine; cancer; translocation; signal transduction; estrogen receptor; integrin-linked kinase; JNK; c-jun; embryonal; alveolar; mTOR; myosin light chain; 0992; 0379; 0307

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Durbin, A. (2010). Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/24739

Chicago Manual of Style (16^th Edition):

Durbin, Adam. “Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma.” 2010. Doctoral Dissertation, University of Toronto. Accessed January 17, 2021. http://hdl.handle.net/1807/24739.

MLA Handbook (7^th Edition):

Durbin, Adam. “Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma.” 2010. Web. 17 Jan 2021.

Vancouver:

Durbin A. Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma. [Internet] [Doctoral dissertation]. University of Toronto; 2010. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1807/24739.

Council of Science Editors:

Durbin A. Studies on Signal Transduction Mechanisms in Rhabdomyosarcoma. [Doctoral Dissertation]. University of Toronto; 2010. Available from: http://hdl.handle.net/1807/24739

Open Access Theses and Dissertations