+publisher:"University of Houston" +contributor:("Webb, Paul")

University of Houston

1. Butler, Ryan 1986-. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.

Degree: PhD, Biology, 2013, University of Houston

URL: http://hdl.handle.net/10657/956

► Ligand-activated transcription factors are a diverse group of proteins that are involved a variety of physiological processes. The purpose of these studies was to investigate… (more)

▼ Ligand-activated transcription factors are a diverse group of proteins that are involved a variety of physiological processes. The purpose of these studies was to investigate the aryl hydrocarbon receptor (AhR) knockout mouse and the effects of hormone replacement therapy on the postmenopausal breast in order to better understand the functions of the ligand-activated transcription factors AhR and estrogen receptor β (ERβ). In the first part of these studies, we investigated the AhR knockout mouse in order to further elucidate the physiological functions of AhR. These mice developed stones in their urinary bladders composed of 100% uric acid while the serum uric acid levels remained normal. We determined these stones were formed by the breakdown of DNA into uric acid from a large number of dying cells. These mice also develop fibrosis of their ventral prostates and a phenotype in the immune system similar to chronic myeloid leukemia. The second part of these studies was to investigate the effects of hormone replacement therapy on the histology and expression of various ligand-activated transcription factors in the postmenopausal breast. We treated postmenopausal women with estrogen or estrogen-progesterone therapy for 3 months and took biopsies of the breasts before and after treatment. Expression of several proteins including AhR, ERα, and ERβ were unchanged after treatment while expression of progesterone receptors was increased. Proliferation and breast density were unchanged by treatment in these breasts; however, we show possible mechanisms leading to proliferation and development of density in non-cancerous breast tissue. In conclusion, these studies revealed a role for AhR in prostatic development, uric acid formation, and leukemia, and have provided new information on the safety of short-term use of HRT. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Warner, Margaret (committee member), Ziburkus, Jokubas (committee member), Webb, Paul (committee member).

Subjects/Keywords: Aryl hydrocarbon receptor; Estrogen receptors; Transcription factors

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APA (6^th Edition):

Butler, R. 1. (2013). Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/956

Chicago Manual of Style (16^th Edition):

Butler, Ryan 1986-. “Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.” 2013. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/956.

MLA Handbook (7^th Edition):

Butler, Ryan 1986-. “Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.” 2013. Web. 25 Jan 2021.

Vancouver:

Butler R1. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/956.

Council of Science Editors:

Butler R1. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/956

University of Houston

2. Jonsson, Philip 1985-. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.

Degree: PhD, Biology, 2014, University of Houston

URL: http://hdl.handle.net/10657/1949

► The estrogen receptors are fundamental factors in human biology. As transcriptional factors regulating gene programs controlling many processes in the body, they are key in… (more)

▼ The estrogen receptors are fundamental factors in human biology. As transcriptional factors regulating gene programs controlling many processes in the body, they are key in both development and disease. Also, as nuclear receptors they can be activated or blocked by specific ligands, making them excellent targets for therapeutics. This dissertation focuses on the study of the estrogen receptors, both the alpha and beta isoforms (ERα and ERβ, respectively), and how they regulate gene transcription in human breast cancer. The proliferative role of ERα in breast cancer remains poorly understood. Here we show that the ion channel KCNK5 is a direct transcriptional target of ERα in breast cancer cell lines MCF7 and T47D. Also, we show that this is reflected by changes in the ion channel’s protein. Furthermore, silencing of the ion channels expression reduces cellular proliferation, as well as the estrogen-induction of proliferation. This uncovers ion channels as potential factors in the proliferation of breast cancer, as well as potential targets in novel treatment approaches. ERα’s role as a transcription factor has predominantly been studied in regards to its regulation of protein-coding genes. Herein, we show that ERα also regulates non-coding RNAs, such as long non-coding RNAs and pseudogenes. We also potentially uncover novel protein-coding targets, by the use of novel RNA- sequencing technology, and the use of microarrays. The other estrogen receptor, ERβ, is less characterized, but it is considered to be anti-proliferative in breast cancer and its activation suggested as a potential future therapy. However, discordant results of expression in breast tumors, correlation to prognosis, and tumor-suppressive function in cell lines have made this a debated field. We explore its role in breast cancer cells further and show that, in certain contexts, ERβ is not able to suppress breast cancer cell proliferation, nor, as often suggested, counteract ERα-mediated signaling. This warrants further studies into whether its activation in breast cancer is a desirable treatment. Advisors/Committee Members: Williams, Cecilia M. (advisor), Gunaratne, Preethi H. (committee member), Webb, Paul (committee member), Willson, Richard C. (committee member).

Subjects/Keywords: Estrogen receptors; Breast cancer

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APA (6^th Edition):

Jonsson, P. 1. (2014). Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1949

Chicago Manual of Style (16^th Edition):

Jonsson, Philip 1985-. “Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.” 2014. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/1949.

MLA Handbook (7^th Edition):

Jonsson, Philip 1985-. “Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.” 2014. Web. 25 Jan 2021.

Vancouver:

Jonsson P1. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/1949.

Council of Science Editors:

Jonsson P1. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/1949

University of Houston

3. Rajapaksa, R. P. Gayani Kumudu 1981-. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.

Degree: PhD, Biology, 2014, University of Houston

URL: http://hdl.handle.net/10657/1919

► Estrogen receptors play a key role in breast cancer, and understanding the mechanisms of action is important in clinical management of the disease. Here we… (more)

▼ Estrogen receptors play a key role in breast cancer, and understanding the mechanisms of action is important in clinical management of the disease. Here we attempted to comprehend the role of the second estrogen receptor (ERβ) in two fundamental cellular mechanisms vital in the development and progression of breast cancer, unfolded protein response (UPR) and epithelial-to-mesenchymal transition (EMT). UPR confers therapeutic resistance and cellular survival in breast cancer in response to endoplasmic reticulum (EnR) stress that is induced by poorly vascularized tumor microenvironment. ERα regulates UPR-driven cell survival; however the role of ERβ is unknown. Here wild-type ERβ (ERβ1) decreased the survival of triple-negative and ERα-positive breast cancer cells in response to pharmacological stress inducers thapsigargin and bortezomib. ERβ1 enhanced cellular apoptosis by down regulating the UPR transducer inositol-requiring enzyme 1 (IRE1) and the splicing of X box-binding protein-1 (XBP-1). Further, expression of ERβ1 in EnR-stressed tamoxifen-resistant cells decreased survival by down regulating the IRE1/XBP-1s pathway. Interestingly, up regulation of ERβ1 increased the sensitivity of tamoxifen-resistant cells to tamoxifen, indicating the role of ERβ1 in regulating resistance of breast cancer to a variety of stressors including anti-estrogens through regulating the UPR. In addition, ERβ1 suppressed the activation of (PKR)-like endoplasmic reticulum kinase (PERK) pathway of UPR in breast cancer cells. Given the association of the PERK pathway with the inhibition of protein synthesis and the activation of pro-survival autophagy, ERβ1 may affect the survival of breast cancer cells by regulating the translational machinery and autophagy. In addition to the down regulation of UPR, ERβ1 was found to imbed EMT and decrease the invasiveness of breast cancer cells. ERβ1 inhibited EMT by up-regulating members of the microRNA-200 family and repressing transcriptional repressors (ZEB1, SIP1) leading to increased expression of epithelial marker E-cadherin. Furthermore, clinical breast cancer specimens showed a positive correlation between ERβ1 and E-cadherin, further supporting that ERβ1 regulates EMT and invasion in breast cancer. The repression of UPR and EMT by ERβ1 strongly supports its tumor suppressive role in breast cancer and suggests its potential utility as a prognostic marker and therapeutic target for the clinical management of the disease. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Thomas, Christoforos (committee member), Gunaratne, Preethi H. (committee member), Williams, Cecilia M. (committee member), Webb, Paul (committee member).

Subjects/Keywords: Breast cancer; ERÎ²; Unfolded protein response; Epithelial-to-mesenchymal transition; Tumor repressor

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APA (6^th Edition):

Rajapaksa, R. P. G. K. 1. (2014). Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1919

Chicago Manual of Style (16^th Edition):

Rajapaksa, R P Gayani Kumudu 1981-. “Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.” 2014. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/1919.

MLA Handbook (7^th Edition):

Rajapaksa, R P Gayani Kumudu 1981-. “Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.” 2014. Web. 25 Jan 2021.

Vancouver:

Rajapaksa RPGK1. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/1919.

Council of Science Editors:

Rajapaksa RPGK1. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/1919

University of Houston

4. Lin, Jean Z. 1984-. Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism.

Degree: PhD, Biology, 2014, University of Houston

URL: http://hdl.handle.net/10657/5359

► Thyroid hormone receptor (TR) activation affects numerous metabolic processes involved in lipid and glucose metabolism, with implications for diseases such as obesity, diabetes, and hyperlipidemia.… (more)

▼ Thyroid hormone receptor (TR) activation affects numerous metabolic processes involved in lipid and glucose metabolism, with implications for diseases such as obesity, diabetes, and hyperlipidemia. Thyroid hormone and synthetic TR agonists are known to decrease serum lipids and induce fat loss. Here we investigate the effects of TR agonists on lipid homeostasis in the liver and adipose tissue. TR agonists lower serum cholesterol levels in rodents, monkeys, and humans. While it is clear that TR activation reduces serum cholesterol, the mechanism behind this effect is less apparent. Although TR agonists have been reported to affect several pathways involved in cholesterol metabolism, the most notable rationale has been that thyroid hormones stimulate expression of the LDL receptor (LDLR). Here we show TR activation can markedly reduce serum cholesterol in mice devoid of LDLR by inducing Cyp7a1 expression and stimulating the conversion and excretion of cholesterol as bile acids. Thus, TR agonists may represent a promising therapeutic to treat hypercholesterolemia disorders for which LDLR induction is not fully effective. Thyroid hormones have long been known to stimulate basal metabolic rate and elicit thermogenesis, effects generally attributed to the activation of brown adipose tissue (BAT). However, the relationship between TR activation and thermogenesis is complex and not fully resolved. Here we show that thyroid hormone and the TR agonist GC-1 induce a BAT-like program of adaptive thermogenesis and uncoupled respiration in subcutaneous white adipose tissue (WAT), which appears to directly mediate an increase in metabolism and marked fat loss. The TR mediated conversion of white to beige fat, an action accompanied by striking anti-diabetic and anti-obesity properties, may represent an unrecognized component of TR-mediated thermogenesis and demonstrates the profound pharmacological potential of beiging of WAT. In conclusion, we have shown that TR activation in the liver reduces serum cholesterol independent of the LDLR via the induction of hepatic Cyp7a1 and that TR activation in WAT elicits a functional conversion of white to brown fat. These data show the TR activation has beneficial effects on lipid homeostasis in the liver and adipose tissue and may suggest an important strategy to combat metabolic diseases. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Moore, David (committee member), Webb, Paul (committee member), Williams, Cecilia M. (committee member), Lin, Chin-Yo (committee member).

Subjects/Keywords: Thyroid hormone; Thyroid hormone receptor; Cholesterol; Thermogenesis

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APA (6^th Edition):

Lin, J. Z. 1. (2014). Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/5359

Chicago Manual of Style (16^th Edition):

Lin, Jean Z 1984-. “Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism.” 2014. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/5359.

MLA Handbook (7^th Edition):

Lin, Jean Z 1984-. “Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism.” 2014. Web. 25 Jan 2021.

Vancouver:

Lin JZ1. Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/5359.

Council of Science Editors:

Lin JZ1. Thyroid Hormone Receptor Regulation of Cholesterol and Lipid Metabolism. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/5359

University of Houston

5. Dey, Prasenjit 1978-. Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer.

Degree: PhD, Biochemistry, 2013, University of Houston

URL: http://hdl.handle.net/10657/955

► High Gleason grade prostate cancers are aggressive. Currently, the major target for treatment is the androgen receptor. Recent literature points towards a tumor suppressive role… (more)

▼ High Gleason grade prostate cancers are aggressive. Currently, the major target for treatment is the androgen receptor. Recent literature points towards a tumor suppressive role of estrogen receptor β (ERβ), which has a potential to be exploited as a target for novel therapeutics used for treatment of prostate cancer. In Chapter 2 of the thesis, we showed that ERβ-selective agonists elicited an increase in apoptosis and this was accompanied by an increase in expression of the pro-apoptotic factor PUMA. Induction of PUMA was dependent on the presence of the transcription factor FOXO3 but was independent of p53. In the ventral prostates of ERβ-/- mice, expression of FOXO3a is lower than that in WT littermates demonstrating a relationship between ERβ and FOXO3a expression found in PC3 and LNCaP cells. Furthermore, in prostate cancers of Gleason grade 4 or higher there was a marked reduction of both ERβ and FOXO3a, while both genes were well expressed in BPH sections. In Chapter 3 of the thesis, we investigated whether the loss of ERβ (also called as ERβ1) and/or expression of its splice variant ERβ2 affected signaling pathways involved in proliferation and bone metastasis of prostate cancer. We found repressed expression of the bone metastasis regulator Runx2 and its target gene, Slug by ERβ1. In addition, the expression of Twist1, a factor whose expression strongly correlates with high Gleason grade prostate cancer, was increased by ERβ2. In terms of cell cycle modification, of the two receptors, ERβ1, but not ERβ2, inhibited proliferation and expression of the proliferation markers Cyclin E, c-Myc, and p45Skp2. Xenograft studies using athymic nude mice confirmed the proliferative effect of ERβ2, as tumors in mice bearing PC3-ERβ2 cells were substantially larger than tumors in mice bearing PC3-control and PC3-ERβ1 cells. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Ström, Anders M. (committee member), Schwartz, Robert J. (committee member), Webb, Paul (committee member), Wang, Yuhong (committee member).

Subjects/Keywords: Prostate cancer; Estrogen receptor beta; Apoptosis; Proliferation; FOXO3a; PUMA; Bone metastasis; Biochemistry

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APA (6^th Edition):

Dey, P. 1. (2013). Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/955

Chicago Manual of Style (16^th Edition):

Dey, Prasenjit 1978-. “Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer.” 2013. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/955.

MLA Handbook (7^th Edition):

Dey, Prasenjit 1978-. “Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer.” 2013. Web. 25 Jan 2021.

Vancouver:

Dey P1. Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/955.

Council of Science Editors:

Dey P1. Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/955

University of Houston

6. Katchy, Anne Chinenye 1984-. Exploring estrogen receptor gene regulatory mechanism in breast cancer.

Degree: PhD, Biochemistry, 2013, University of Houston

URL: http://hdl.handle.net/10657/1061

► Estrogen has vital roles in development and maintenance of mammary gland and supports the growth of the majority of primary breast cancer. It carries out… (more)

▼ Estrogen has vital roles in development and maintenance of mammary gland and supports the growth of the majority of primary breast cancer. It carries out its function through the estrogen receptors (ER): ERα and ERβ. In this dissertation, we focused on identifying the functional and genome wide effects of both receptors in breast cancer cell lines (T47D and MCF7). First, we aimed at identifying microRNAs (miRNAs) that are significantly associated with normal or disrupted estrogen signaling in breast cancer cells, and are regulated by ERα and ERβ. Despite the fact that 24h estrogen treatment results in strong changes to expression of about 900 protein-coding transcripts, we found no significant changes in mature miRNA expression levels by 17β-estradiol (E2)-activated ERα in neither T47D nor MCF7 breast cancer cells. On the other hand, when studying the effects of exogenously expressed ERβ, we identified miR-135a, miR-21, miR-200c, and miR-522, among others, as being regulated. Most of the ERβ effects were ligand-independent, but we observed a significant response to E2 in the MCF7-ERβ cells. Also, the MCF7-ERβ showed enhanced stem cell abilities in comparison to the MCF7-Control cells as illustrated by increased mammospheres formation during several generations. Secondly, we aimed at investigating environmental factors and its effect on the risk for breast cancer. We identified the gene expression response for each of these compounds: BPA, genistein (Gen), E2, and soy formula extract (SF) in MCF7 cells, and found that each regulated similar genes in the same manner. Many target genes regulated by BPA, Gen, and SF, were involved in important biological processes identical to those of estrogen. Investigation of non-ERα mediated regulations for these EDCs suggested that these compounds may regulate gene transcription solely through ERα, in the cells and doses used. Furthermore, we found that these compounds acted together in a sub-additive manner, and tumor clustering with the gene expression profile of these EDC compounds revealed a significantly lower disease free survival. Altogether, the data presented in this dissertation would aid in increasing the knowledge of early risk factors for breast cancer. Our work provides data for future use of the estrogen receptors in clinical applications by providing new candidates for pharmaceutical drug development, as well as, biomarkers for diagnosis and prognosis. Advisors/Committee Members: Williams, Cecilia M. (advisor), Schwartz, Robert J. (committee member), Webb, Paul (committee member), Gao, Xiaolian (committee member).

Subjects/Keywords: Estrogen receptors; MicroRNAs (miRNA); Breast cancer; Bisphenol A; Phytoestrogen; Biochemistry

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APA (6^th Edition):

Katchy, A. C. 1. (2013). Exploring estrogen receptor gene regulatory mechanism in breast cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1061

Chicago Manual of Style (16^th Edition):

Katchy, Anne Chinenye 1984-. “Exploring estrogen receptor gene regulatory mechanism in breast cancer.” 2013. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/1061.

MLA Handbook (7^th Edition):

Katchy, Anne Chinenye 1984-. “Exploring estrogen receptor gene regulatory mechanism in breast cancer.” 2013. Web. 25 Jan 2021.

Vancouver:

Katchy AC1. Exploring estrogen receptor gene regulatory mechanism in breast cancer. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/1061.

Council of Science Editors:

Katchy AC1. Exploring estrogen receptor gene regulatory mechanism in breast cancer. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/1061

University of Houston

7. Carruthers, Carl W., Jr. 1971-. Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity.

Degree: PhD, Biochemistry, 2014, University of Houston

URL: http://hdl.handle.net/10657/1918

► The glucocorticoid receptor (GR) N-terminal domain (NTD) contains a transactivation domain (activation function 1; AF-1). Although GR AF-1 is phosphorylated, effects of GR phosphorylation upon… (more)

Subjects/Keywords: Phosphorylation; Glucocorticoids; Glucocorticoid receptors; Tau1c; Transactivation; CBP; Transcriptional adaptor zinc binding (TAZ) 2

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APA (6^th Edition):

Carruthers, Carl W., J. 1. (2014). Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1918

Chicago Manual of Style (16^th Edition):

Carruthers, Carl W., Jr 1971-. “Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity.” 2014. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/1918.

MLA Handbook (7^th Edition):

Carruthers, Carl W., Jr 1971-. “Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity.” 2014. Web. 25 Jan 2021.

Vancouver:

Carruthers, Carl W. J1. Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/1918.

Council of Science Editors:

Carruthers, Carl W. J1. Phosphorylation of Glucocorticoid Receptor tau1c Transactivation Domain Enhances Binding to CREB Binding Protein (CBP) TAZ2 and a Microfluidic, High Throughput Protein Crystal Growth Method for Microgravity. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/1918

University of Houston

8. Pinto, Caroline Lucia 1981-. In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling.

Degree: PhD, Biochemistry, 2014, University of Houston

URL: http://hdl.handle.net/10657/4737

► Humans are exposed daily to cocktails of chemicals from different sources. Some of these chemicals can interfere with hormonal signaling, and are referred to as… (more)

▼ Humans are exposed daily to cocktails of chemicals from different sources. Some of these chemicals can interfere with hormonal signaling, and are referred to as endocrine disrupting chemicals (EDCs). A mechanism through which EDCs may act is by binding and modulating the activity of nuclear receptors (NRs), which could lead to adverse health outcomes, especially during critical developmental windows, such as fetal development and perinatal life. As we are exposed to chemical cocktails, there is an increased concern regarding adverse effects resulting from exposures to combinations of EDCs. Mixture effects of bisphenol A and phytoestrogens, well-known xenoestrogens, were assessed in transactivation assays mediated by the estrogen receptors (ERs) and in MCF-7 cell proliferation assays. We observed additive effects with a combination of nanomolar concentrations of these chemicals, levels that are relevant to human exposure. Another major concern is the need to refine, reduce and replace animal models, and zebrafish have been used as an alternative in vivo model. However, to support zebrafish for risk assessment of EDCs, it is crucial to evaluate the transcriptional activity/selectivity of mammalian NR ligands towards their zebrafish homologues. By using stable reporter cell lines expressing human or zebrafish NRs, we observed clear differences in the selectivity/activity of ER and peroxisome-proliferator activated receptor gamma (PPARg) ligands between human and their zebrafish counterparts, demonstrating the importance of assessing the transcriptional profile of EDCs prior to using them in vivo. Liver X receptors (LXRs), also NRs, are key regulators of lipid and cholesterol metabolism in mammals. Transcriptomic analysis of zebrafish larvae treated with the mammalian LXR agonists T0901317 and GW3965, also activators of zebrafish LXR, revealed a primary role of LXR in regulating lipid metabolism and transport during zebrafish development. Tissue enrichment analysis predicted the liver, the yolk syncytial layer and the eye to be affected by LXR activation in zebrafish, which correlated with increased lipid uptake from the yolk, and with morphological abnormalities in the retina and lens of developing zebrafish. The expression of important genes for eye development and maintenance of photoreceptors, was modulated in zebrafish exposed to the ligands as well as in LXR knockout mice, revealing, for the first time, a new potential physiological role of LXRs in regulating expression of gene networks important for visual function in vertebrates. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Bondesson, Maria (committee member), Fox, Robert O. (committee member), Eichberg, Joseph (committee member), Bark, Steven J. (committee member), Webb, Paul (committee member).

Subjects/Keywords: Zebrafish; Nuclear receptors; Estrogen receptors; Liver X receptor; Peroxisome proliferator-activated receptor gamma; Endocrine disruptors; Lipid metabolism; Lipids; Yolk; Retina; Lenses; Eye

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APA (6^th Edition):

Pinto, C. L. 1. (2014). In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4737

Chicago Manual of Style (16^th Edition):

Pinto, Caroline Lucia 1981-. “In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling.” 2014. Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/4737.

MLA Handbook (7^th Edition):

Pinto, Caroline Lucia 1981-. “In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling.” 2014. Web. 25 Jan 2021.

Vancouver:

Pinto CL1. In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/4737.

Council of Science Editors:

Pinto CL1. In Vitro Assays and Zebrafish as an in Vivo Model to Study Nuclear Receptor Signaling. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/4737

University of Houston

9. Nikollo, Foti 1986-. Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer.

Degree: PhD, Biochemistry, University of Houston

URL: http://hdl.handle.net/10657/2043

► Estrogens represent a subclass of steroid hormones that by regulating cell growth and differentiation, influence normal physiology as well as pathology. The effects of estrogen… (more)

▼ Estrogens represent a subclass of steroid hormones that by regulating cell growth and differentiation, influence normal physiology as well as pathology. The effects of estrogen are mediated by two members of the nuclear receptor superfamily, Estrogen Receptor α (ERα) and ERβ. A plethora of studies have shown that ERα and ERβ exert opposite effects on cancer development and progression by eliciting distinct transcriptional responses and differentially influencing cellular processes such as cell proliferation, apoptosis, and migration. The present study focused on the potential role of ERβ in affecting development and progression of the two most commonly diagnosed cancers in men and women, lung and breast cancer, respectively. Our studies revealed that upregulation of wild-type ERβ (ERβ1), but not the splice variant ERβ2, reduces proliferation and enhances apoptosis in non-small cell lung cancer (NSCLC) cells. ERβ1 was found to induce apoptosis by stimulating the intrinsic apoptotic pathway that involved upregulation of the pro-apoptotic factor BIM and downregulation of components of the growth factor signaling pathway. Manipulation of EGFR and RAS expression and activity in ERβ1-expressing cells revealed the central role of oncogenic RAS signaling in ERβ1-mediated pro-apoptotic phenotype and EGFR regulation. In addition, our studies demonstrated that ERβ1 sensitizes NSCLC cells to chemotherapeutic agents. Upregulation of ERβ1 decreased the viability of doxorubicin- and etoposide-treated NSCLC cells by inducing G2/M phase cell cycle arrest. In response to treatment, ERβ1-expressing cells had increased p-Chk1 levels, an indicator of activated DNA damage response, compared with the control cells. Finally, we showed that ERβ1 represses epithelial to mesenchymal transition (EMT) and invasion of basal-like breast cancer cells both in vitro and in vivo. ERβ1 impeded EMT by downregulating EGFR. EGFR downregulation in ERβ1-expressing cells was associated with the stabilization of the ubiquitin ligase c-Cbl-EGFR complexes that led to increased ubiquitylation and degradation of the activated receptor. In conclusion, our studies have unveiled the important role of ERβ in regulating crucial processes of lung and breast cancer development and progression and propose ERβ as a potential biomarker for predicting metastasis in breast cancer and response to treatment in NSCLC. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Thomas, Christoforos (committee member), Schwartz, Robert J. (committee member), Frigo, Daniel E. (committee member), Webb, Paul (committee member).

Subjects/Keywords: Estrogen receptor beta; EGFR; NSCLC; RAS; DNA damage response; P53; EMT; Basal-like; E-cadherin

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APA (6^th Edition):

Nikollo, F. 1. (n.d.). Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/2043

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Chicago Manual of Style (16^th Edition):

Nikollo, Foti 1986-. “Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer.” Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/2043.

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MLA Handbook (7^th Edition):

Nikollo, Foti 1986-. “Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer.” Web. 25 Jan 2021.

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No year of publication.

Vancouver:

Nikollo F1. Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/2043.

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

Council of Science Editors:

Nikollo F1. Exploring the Tumor Suppressive Roles of Estrogen Receptor β in Lung and Breast Cancer. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/2043

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

University of Houston

10. Bado, Igor Landry 1986-. Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer.

Degree: PhD, Biology, University of Houston

URL: http://hdl.handle.net/10657/3620

► Breast cancer is a heterogeneous disease with regard to clinical outcome and molecular characteristics. Some breast cancers are more aggressive because they express mutant proteins… (more)

▼ Breast cancer is a heterogeneous disease with regard to clinical outcome and molecular characteristics. Some breast cancers are more aggressive because they express mutant proteins with potent oncogenic functions including mutant p53 proteins with gain of functions. Such tumors are often resistant to therapies. Accumulating data show positive correlations between ERβ1 and better survival, indicating more important roles of the receptor in breast cancer. First, we investigated the role of ERβ in triple negative breast cancer cells (TNBCs) that are mutant for p53. These cells are derived from very aggressive cancers with highly metastatic and chemoresistant properties. TNBC are negative for ERα, PR, and Her2, and there is no effective targeted therapy. Despite the lack of ERα, a significant number of TNBCs express ERβ. ERβ1 displays anti-migratory, anti-invasive, and anti-metastatic properties. However, the mechanism underlying its function is not well understood. Using molecular technics, we found that ERβ1 opposes mutant p53 gain-of-function through direct interaction. Most importantly, we found that ERβ1 can use mutant p53 as a co-factor to alter gene transcription. Further, the ERβ1-induced epithelial transformation was p63-dependent, suggesting an association between ERβ1, mutant p53 and p63. Second, we investigated the role of ERβ in ERα-positive breast cancer cells. These cells are derived from less aggressive tumors that respond better to hormonal therapy. ERα-positive breast cancers often express wild-type p53, yet p53 tumor suppressive function is inactivated. Several factors including ERα have been found to inhibit wild-type p53 activity. Previous studies have shown anti-proliferative responses following upregulation of ERβ1 in ERα-positive breast cancer cells. ERβ1 was also shown to correlate with better overall and disease-free survival in patients with ERα-positive breast cancer especially after hormonal therapy. Still, the mechanism through which ERβ1 associates with improved prognosis had yet to be investigated. We show that ERβ1 enhances wild-type p53 activity in ERα-positive cells. Further, we found that ERβ1-specific ligands can affect p53 transcriptional activity. Overall, we were able to suggest some novel mechanisms through which ERβ1 elicits its tumor suppressive function and propose ERβ1 as a potential good marker and target for breast cancer treatment. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Thomas, Christoforos (committee member), Webb, Paul (committee member), Lin, Chin-Yo (committee member), Frigo, Daniel E. (committee member).

Subjects/Keywords: Breast cancer; Cancer; Triple negative breast cancer cells (TNBC); ERβ1; P53; P63; EMT; Invasion; Metastasis; Luminal breast cancer; ERα

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

APA (6^th Edition):

Bado, I. L. 1. (n.d.). Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/3620

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

Chicago Manual of Style (16^th Edition):

Bado, Igor Landry 1986-. “Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer.” Doctoral Dissertation, University of Houston. Accessed January 25, 2021. http://hdl.handle.net/10657/3620.

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

MLA Handbook (7^th Edition):

Bado, Igor Landry 1986-. “Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer.” Web. 25 Jan 2021.

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

Vancouver:

Bado IL1. Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10657/3620.

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

Council of Science Editors:

Bado IL1. Understanding the Tumor Suppressive Functions of Estrogen Receptor β in Breast Cancer. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/3620

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

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