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1.
Vaz, Cátia Alexandra Vicente.
Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines.
Degree: 2010, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/2292 
► Regucalcin (RGN) is a calcium-binding protein playing an important role in maintenance of intracellular calcium homeostasis. Because of its diminished expression with aging it is…
(more)
▼ Regucalcin (RGN) is a calcium-binding protein playing an important role in maintenance of intracellular calcium homeostasis. Because of its diminished expression with aging it is also designated Senescence-marker-protein (SMP30). In addition, RGN suppresses cell proliferation, inhibits expression of oncogenes, and increases the expression of tumor suppressor genes in hepatoma cell lines. Very recently, our research group demonstrated that RGN expression is diminished in prostate cancer tissues, what suggests that RGN may have a protective role against carcinogenesis and, consequently, loss of regucalcin expression may contribute to tumor development. The present project aims to characterize RGN expression in prostate tissues and cell-lines and to determine the role of RGN on the expression of oncogenes and tumour suppressor genes in neopasic and non-neoplasic prostate cells. The expression of RGN in rat prostate at different post-natal ages determined by quantitative PCR analysis showed a significant increase at 3M old rats, maintaining their expression in 6M-old animals and diminishing in the following stages. In this report, we confirmed RGN protein expression in human cancer prostate tissues, and cells lines by Imunohistochemistry and Western Blot, respectively. To analyze the effect of RGN on the expression of oncogenes (BCL2, Ha-ras and c-myc) and tumor supressor genes (p53 and RB1), pIRES/RGN expression vectors were constructed and used to transfect LnCAP, PC3, PNT1A and PNT2 cells. Fluorescence microscopy analysis showed successful transfection of PC3 and PNT1A cells, with RGN-GFP protein localization in cell nuclei and cytoplasm. Analysis of transfection experiments in LnCAP and PNT2 cells, and determination of the effect of RGN on the expression of tumor related genes are underway. Nevertheless, RGN localization in cell nuclei, suggests their likely influence regulating expression of oncogenes and tumor suppressor genes in prostate cell lines overexpressing RGN.
Advisors/Committee Members: Socorro, Sílvia Cristina da Cruz Marques.
Subjects/Keywords: Genes supressores de tumores; Oncogenes - Regucalcina; Cancro da prostata - Regucalcina - Genes supressores de tumor
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APA (6th Edition):
Vaz, C. A. V. (2010). Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines. (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/2292
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vaz, Cátia Alexandra Vicente. “Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines.” 2010. Thesis, RCAAP. Accessed January 23, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/2292.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vaz, Cátia Alexandra Vicente. “Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines.” 2010. Web. 23 Jan 2021.
Vancouver:
Vaz CAV. Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines. [Internet] [Thesis]. RCAAP; 2010. [cited 2021 Jan 23].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/2292.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vaz CAV. Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines. [Thesis]. RCAAP; 2010. Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/2292
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
Rodrigues, Daniel Barreira.
Regucalcin regulation by extracellular calcium in prostate cells.
Degree: 2012, Universidade da Beira Interior
URL: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/1117
► Prostate cancer is one of the most diagnosed diseases in men at the present time. It is well known that changes in calcium (Ca2+) homeostasis…
(more)
▼ Prostate cancer is one of the most diagnosed diseases in men at the present time. It is well
known that changes in calcium (Ca2+) homeostasis are derived from modifications in Ca2+
regulating elements. Regucalcin (RGN) is a Ca2+-binding protein which plays an important role
in maintenance of intracellular Ca2+ homeostasis and regulation of apoptosis and
proliferation. RGN is underexpressed in prostate cancer cells, suggesting that a loss of RGN
expression may be associated with tumor development. In vivo studies have also shown that
Ca2+ administration acts as a regulator of RGN expression in liver and kidney tissues. However,
no studies on the characterization of RGN regulation by extracelular Ca2+ in prostate cells
have been conducted. To attain this goal, prostate cells were stimulated with different doses
of CaCl2 during several periods of time. To assess RGN mRNA and protein expression, Real
Time PCR and Western Blot were carried out, respectively. Moreover, the cell viability in
response to treatments was evaluated through MTS assays. Our results show that nonneoplastic
PNT1A cells present higher levels of RGN when compared to neoplastic LNCaP or
PC3 cells. We also verified that RGN expression in PNT1A cells is up-regulated by extracellular
Ca2+ at 1,5h after stimuli, but its expression decreases after 3h of stimulation. We also
showed that high doses of extracellular Ca2+ induce different effects on cell proliferation
between PNT1A and LNCaP cells. This study led us to conclude that RGN appears to be
regulated by extracellular Ca2+ levels in prostate cells and that an elevation of extracellular
Ca2+ promotes high rates of cell proliferation in LNCaP cells, possibly due to the
down-regulation in RGN expression in cancer cells.
Subjects/Keywords: Cancro da próstata; Regucalcina; Cancro da próstata - Cálcio; Receptor sensível do cálcio
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APA (6th Edition):
Rodrigues, D. B. (2012). Regucalcin regulation by extracellular calcium in prostate cells. (Thesis). Universidade da Beira Interior. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/1117
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rodrigues, Daniel Barreira. “Regucalcin regulation by extracellular calcium in prostate cells.” 2012. Thesis, Universidade da Beira Interior. Accessed January 23, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/1117.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rodrigues, Daniel Barreira. “Regucalcin regulation by extracellular calcium in prostate cells.” 2012. Web. 23 Jan 2021.
Vancouver:
Rodrigues DB. Regucalcin regulation by extracellular calcium in prostate cells. [Internet] [Thesis]. Universidade da Beira Interior; 2012. [cited 2021 Jan 23].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/1117.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rodrigues DB. Regucalcin regulation by extracellular calcium in prostate cells. [Thesis]. Universidade da Beira Interior; 2012. Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/1117
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
3.
Correia, Sara Carina de Lima.
Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death".
Degree: 2014, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3987
► Spermatogenesis is the intricate and coordinated process by which thousands of spermatozoa are produced daily within the male gonad. In addition, mammalian testis also serves…
(more)
▼ Spermatogenesis is the intricate and coordinated process by which thousands of spermatozoa
are produced daily within the male gonad. In addition, mammalian testis also serves as an
endocrine organ, producing the sex steroid hormones needed for normal spermatogenesis and
development of male phenotype. Over the years, estrogens have emerged as important
regulators of male reproductive function, but their role in spermatogenesis has remained a
matter of controversy. There are reports indicating that estrogens are survival factors for
germ cells, while other strong evidences associated their actions with testicular apoptosis and
diminution of germ cell number. Furthermore, the molecular targets underpinning the
survival or apoptotic effects of estrogens in mammalian testis remain to be fully elucidated.
Regucalcin (RGN) is a calcium (Ca2+)‐binding protein playing an important role in the
maintenance of intracellular Ca2+ homeostasis, for which a role in spermatogenesis has been
suggested. RGN was identified in male reproductive tract tissues, being described as an
estrogen‐target gene in rat and human prostate cells, and as an androgen‐target gene in the
testis. However, the effect of estrogens controlling the expression levels of RGN in the testis
is entirely unknown. Noteworthy, it has been indicated the role of RGN in the control of cell
survival and apoptosis, and its antioxidant properties also have been reported. Although a
tight control of apoptosis and oxidative stress are of the paramount importance for proper
testis function, the role of RGN in testicular physiology has not deserved attention yet. Sperm
undergo maturation acquiring progressive motility and the capacity to fertilize oocyte only
during passage through the epididymis. Although a gradient of Ca2+ along the epididymis has
been described, its effects on epididymal function remain poorly explored.
The main objective of this thesis is to disclose the relationship between estrogens and
apoptosis of germ cells, including the regulatory effects of these sex steroid hormones on the
testicular expression of RGN. Secondly, the role of RGN in regulating apoptosis and oxidative
stress in the testis, as well as, in sperm maturation in epididymis will be explored.
A 100 nM dose of 17β‐estradiol (E2), mimicking the elevated concentrations of estrogens found
in the testis of infertile patients, induced apoptosis of germ cells and decreased cell
proliferation, which was accompanied by disrupted expression of the SCF/c‐kit system. E2‐
stimulation also increased RGN expression, suggesting that the augmented expression of this
protein may be a mechanism to counteract E2‐induced apoptosis. Concerning the function of
RGN in modulation of apoptosis in the testis, it was shown that RGN plays a pivotal role
rescuing cells from apoptosis induced by noxious stimuli. Moreover, RGN overexpression led to
increased protection against oxidative stress in the testis, which further confirmed the
cytoprotective role of RGN. The results presented herein also demonstrated the…
Advisors/Committee Members: Socorro, Sílvia Cristina da Cruz Marques, Cavaco, José Eduardo Brites, van Pelt, Anna Maria Margaretha.
Subjects/Keywords: Sistema reprodutor masculino; Espermatogénese; Infertilidade masculina; Regucalcina; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
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APA ·
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Manager
APA (6th Edition):
Correia, S. C. d. L. (2014). Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death". (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3987
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Correia, Sara Carina de Lima. “Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death".” 2014. Thesis, RCAAP. Accessed January 23, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3987.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Correia, Sara Carina de Lima. “Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death".” 2014. Web. 23 Jan 2021.
Vancouver:
Correia SCdL. Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death". [Internet] [Thesis]. RCAAP; 2014. [cited 2021 Jan 23].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3987.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Correia SCdL. Estrogens and regucalcin in testicular apoptosis and sperm function: “a matter of life and death". [Thesis]. RCAAP; 2014. Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3987
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
4.
Cardoso, Henrique José Matos Morão Mingote.
The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?.
Degree: 2014, RCAAP
URL: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/5705
► The progression of prostate cancer (PCa), from an early stage confined to prostate to a more aggressive form, is associated with loss of androgen responsiveness.…
(more)
▼ The progression of prostate cancer (PCa), from an early stage confined to prostate to a
more aggressive form, is associated with loss of androgen responsiveness. At this stage, PCa
cells proliferate independently of androgens actions (the so-called hormone refractory
prostate cancer, HRPC), which cause the failure of classical androgen ablation therapies and
restricts the therapeutic options for this usually lethal form of disease. Imatinib mesylate is a
chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT receptors among
others, and has been successfully used to treat leukemias and gastrointestinal stromal
tumors. However, its application for treatment of PCa has not been totally effective with
preclinical models and clinical experimentation producing discordant results. On the other
hand, regucalcin (RGN), a calcium (Ca2+)-binding protein that regulates intracellular Ca2+
homeostasis and the activity of several proteins involved in intracellular signaling pathways,
namely, kinases and phosphatases, has been associated with suppression of cell proliferation
in rat prostate. These raised the question whether RGN may regulate the expression of c-KIT
and its ligand, the stem cell factor (SCF). Therefore, the present dissertation firstly aimed to
analyze the cytotoxic effects of imatinib in two cell line models of HRPC, DU145 and PC3
cells. Moreover, the effect of RGN on the expression of SCF/c-KIT in rat prostate was
evaluated by means of a transgenic animal model overexpressing RGN (Tg-RGN). Finally, the
subcellular localization of RGN in HRPC cell lines and its association with a-tubulin was
investigated. DU145 and PC3 cells were incubated with 20 µM imatinib for 48 and 72 hours.
The MTS assay was used to assess cell viability in response to imatinib and the colorimetric
measurement of the enzymatic activity of caspase-3 was included as an end-point of
apoptosis. The expression of cell-cycle and apoptosis regulators in response to imatinib, and
the expression of SCF/c-KIT in Tg-RGN vs. wild-type rats were determined by real-time PCR
and Western Blot. The expression of RGN in HRPC cells lines in its association with a-tubulin
were evaluated through fluorescent immunocytochemistry. Treatment with imatinib
decreased the viability of DU145 cells at 48 and 72 hours. Although imatinib decreased the
viability of PC3 cells upon 6 hours of treatment, thereafter cell viability significantly
increased in relation to control. Accordingly, the enzymatic activity of caspase-3 was
increased in DU145 cells whereas diminished activity of caspase-3 was observed in PC3 cells
treated with imatinib for 48 and 72 hours. Moreover, DU145 cells displayed reduced
expression of anti-apoptotic protein Bcl-2 and increased levels of the executioners of
apoptosis caspase-8 and caspase-9. No differences were observed on the expression levels of
these apoptosis related proteins in PC3 cells. The mRNA expression of cell cycle inhibitor p21
was increased in both DU145 and PC3 cells. Also, the mRNA levels of VEGF were decreased in…
Advisors/Committee Members: Maia, Cláudio, Socorro, Silvia Cristina da Cruz Marques.
Subjects/Keywords: Cancro da Próstata; Du145; Imatinib; Pc3; Regucalcina; Sistema Scf/C-Kit; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cardoso, H. J. M. M. M. (2014). The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?. (Thesis). RCAAP. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/5705
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cardoso, Henrique José Matos Morão Mingote. “The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?.” 2014. Thesis, RCAAP. Accessed January 23, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/5705.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cardoso, Henrique José Matos Morão Mingote. “The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?.” 2014. Web. 23 Jan 2021.
Vancouver:
Cardoso HJMMM. The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?. [Internet] [Thesis]. RCAAP; 2014. [cited 2021 Jan 23].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/5705.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cardoso HJMMM. The SCF/c-KIT system and imatinib actions in prostate cancer: a cross-talk with RGN?. [Thesis]. RCAAP; 2014. Available from: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/5705
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
5.
Vaz, Cátia Alexandra Vicente.
Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis.
Degree: 2015, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3988
► Prostate Cancer (PCa) is one of the most common cancers in men and continues to be a source of considerable morbidity and mortality worldwide. The…
(more)
▼ Prostate Cancer (PCa) is one of the most common cancers in men and continues to be a source of considerable morbidity and mortality worldwide. The progression of PCa from an early stage, confined to prostate, to a more aggressive phenotype is characterized by the loss of androgen-responsiveness, which means that tumor cells gain the ability to growth independently of the circulating androgens. Furthermore, the neoplastic transformation of prostate cells and tumor progression to more aggressive stages require several genetic and metabolic alterations. Warburg firstly demonstrated that tumor cells predominantly use glycolysis for obtaining energy in detriment of oxidative phosphorylation, with the production of high amounts of lactate. This metabolic adaptation is common to the majority of cancers and is now established as a hallmark of cancer. However, the alterations in the glycolytic metabolism that occur in the progression to the androgen-independent stage of PCa as well as the role of androgens in regulating the glycolytic flux are poorly studied.
Regucalcin (RGN) is a calcium (Ca2+)-binding protein that plays a determinant role in the maintenance of intracellular Ca2+ homeostasis. RGN also has been suggested as a tumor suppressor protein, since it is involved in the regulation of proliferation, apoptosis, and diverse metabolic pathways, and its antioxidant properties also have been reported. In addition, androgens, Ca2+ and age, all well-known factors implicated in PCa development, regulate RGN expression in different tissues but their action in prostate remains to be elucidated. It was also demonstrated that RGN is under expressed in human PCa cases comparatively to normal tissues, which suggest that the loss of RGN may be an event favoring tumor development. Moreover, considering the biological processes under the influence of RGN it is also predictable that it may exert a crucial role in the maintenance of cell tissue homeostasis. Notwithstanding, little is known about the factors that regulate RGN expression in the prostate, and no studies exist regarding the role of RGN in the regulation of cell proliferation, apoptosis, Ca2+ homeostasis, and metabolism in this tissue.
The present thesis firstly established the glycolytic profile of androgen-responsive (LNCaP) and non-responsive (PC3) PCa cells. We demonstrated that LNCaP and PC3 cells display a distinct glycolytic profile, with PC3 presenting higher production and export of lactate as a result of increased expression of target regulators of this metabolic pathway. The role of androgens in the regulation of the glycolytic flux in PCa cells was also studied. Treatment of LNCaP cells with 5α-dihydrotestosterone (DHT, 10nM) significantly increased glucose uptake, glycolysis rate and the export of lactate by upregulating the expression of important regulators of glycolysis, in a mechanism that seems to involve the androgen receptor (AR). These results highlighted the importance of controlling glucose and lactate metabolism as possible therapeutic approaches in…
Advisors/Committee Members: Socorro, Sílvia Cristina da Cruz Marques, Baptista, Cláudio Jorge Maia.
Subjects/Keywords: Cancro da próstata - Terapêutica; Metabolismo glicolítico; Regucalcina; Apoptose; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
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APA ·
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MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vaz, C. A. V. (2015). Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis. (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3988
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vaz, Cátia Alexandra Vicente. “Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis.” 2015. Thesis, RCAAP. Accessed January 23, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3988.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vaz, Cátia Alexandra Vicente. “Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis.” 2015. Web. 23 Jan 2021.
Vancouver:
Vaz CAV. Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis. [Internet] [Thesis]. RCAAP; 2015. [cited 2021 Jan 23].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3988.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vaz CAV. Androgens and calcium-binding protein regucalcin in the control of prostate cells metabolism and survival: implications in carcinogenesis. [Thesis]. RCAAP; 2015. Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/3988
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
6.
Silva, Ana Manuela dos Santos.
The protective effect of regucalcin against radiation-induced testicular damage.
Degree: 2015, RCAAP
URL: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/6061
► Testicular cancer is the most common malignancy among young men, and radiation therapy is a generally used as treatment. However, the exposure to radiation has…
(more)
▼ Testicular cancer is the most common malignancy among young men, and radiation therapy is a generally used as treatment. However, the exposure to radiation has several adverse effects on male fertility. Considering the high survival rates and the age of incidence of this malignancy, it is mandatory to identify effective strategies protecting against radiation-induced testicular damage. Regucalcin (RGN) is a calcium (Ca2+)-binding protein that is broadly expressed in the male reproductive tract. Several studies have demonstrated RGN ability suppressing cell death in different cell types. Previously, our research group showed that RGN overexpression had beneficial effects on spermatogenesis by suppressing chemical-induced apoptosis. Moreover, RGN is upregulated in radioresistant cell lines, suggesting that it also can protect from radiation damage. The present work aimed to evaluate whether RGN may play a role in spermatogenesis recovery after radiation treatment. For this purpose, transgenic rats overexpressing RGN (Tg-RGN) and their wild-type (Wt) counterparts were exposed to X-rays. At ten weeks of recovery after irradiation, the testicular status and the epididymal sperm parameters were evaluated. The expression of RGN and several cell cycle and apoptosis regulators was also evaluated. In addition, the enzymatic activity of caspase-3 was measured. Upon radiation treatment and ten weeks of recovery, both the testicular status and sperm parameters seem to have been less affected by X-rays in Tg-RGN. We also found a diminished expression of p53 and p21, which may indicate the reinitiating of spermatogenesis. Moreover, the reduced activity of caspase-3 detected in Tg-RGN is in accordance with low levels of caspase-8 and increased Bcl-2/Bax ratio, suggesting that these animals are more resistant to testicular apoptosis in response to radiation. RGN expression was significantly enhanced in Wt rats after irradiation, supporting its involvement in the anti-apoptotic response. Altogether, the present findings point out a protective role for RGN overexpression against radiation-induced testicular damage.
O cancro testicular é a malignidade masculina mais frequente nos jovens, e a radioterapia é normalmente usada no seu tratamento. No entanto, a exposição à radiação tem vários efeitos secundários na fertilidade masculina, tornando-se necessária a identificação de estratégias efectivas para a proteger do dano testicular provocado pela radioterapia. A regucalcina (RGN) é uma proteína de ligação ao cálcio (Ca2+) que se encontra amplamente expressa no tracto reprodutor masculino. Vários estudos demonstraram a capacidade supressora da RGN na morte celular de diferentes tipos de células. Anteriormente, o nosso grupo de investigação mostrou que a sobre-expressão de RGN teve efeitos benéficos na espermatogénese por suprimir a apoptose induzida quimicamente. Para além disso, a RGN é regulada positivamente em linhas celulares radiorresistentes, sugerindo que esta pode proteger de danos causados pela radiação. O presente trabalho…
Advisors/Committee Members: Batista, Cláudio Jorge Maia, Socorro, Sílvia.
Subjects/Keywords: Apoptose; Dano Testicular; Epidídimo; Espermatogénese; Espermatozóides; Oncofertilidade Masculina; Preservação da Fertilidade; Radioterapia; Regucalcina; Testículo; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
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APA ·
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MLA ·
Vancouver ·
CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, A. M. d. S. (2015). The protective effect of regucalcin against radiation-induced testicular damage. (Thesis). RCAAP. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/6061
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Silva, Ana Manuela dos Santos. “The protective effect of regucalcin against radiation-induced testicular damage.” 2015. Thesis, RCAAP. Accessed January 23, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/6061.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Silva, Ana Manuela dos Santos. “The protective effect of regucalcin against radiation-induced testicular damage.” 2015. Web. 23 Jan 2021.
Vancouver:
Silva AMdS. The protective effect of regucalcin against radiation-induced testicular damage. [Internet] [Thesis]. RCAAP; 2015. [cited 2021 Jan 23].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/6061.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Silva AMdS. The protective effect of regucalcin against radiation-induced testicular damage. [Thesis]. RCAAP; 2015. Available from: https://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/6061
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
7.
Marques, Ricardo Jorge Fernandes.
Biological evidence of the protective role of regucalcin in breast cancer.
Degree: 2016, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/4214
► O cancro da mama é uma doença heterogénea que compreende uma grande variedade de alterações moleculares e diferentes tipos de resposta em termos clínicos. Esta…
(more)
▼ O cancro da mama é uma doença heterogénea que compreende uma grande variedade de alterações moleculares e diferentes tipos de resposta em termos clínicos. Esta diversidade reside nos múltiplos fatores que podem levar à transformação maligna das células, em consequência da desregulação de diferentes processos fisiológicos.
A
regucalcina (RGN) é uma proteína de ligação ao cálcio (Ca2+) e cuja principal função conhecida é regular a homeostase do Ca2+ intracelular, mas podendo também estar envolvida na regulação da proliferação celular, apoptose e metabolismo das células. A RGN também foi identificada como um gene regulado por hormonas, incluindo os esteroides sexuais como os androgénios. Para além disso, foi anteriormente associada a determinadas patologias e tendo mesmo sido identificada como uma proteína subexpressa em casos humanos de cancro da mama, próstata ou fígado. No fígado, a subexpressão da RGN foi detetada em lesões pré-neoplásicas, ou seja, antes da aquisição do fenótipo neoplásico, o que sugere que a sua diminuição pode estar ligada ao início do processo de transformação tumorigénico. Apesar destas evidências, os mecanismos moleculares subjacentes às funções da RGN na mama permanecem por identificar. Nesta tese, colocámos a hipótese de que a sobreexpressão da RGN poderá exercer uma ação protetora em relação à carcinogénese mamária. De modo a avaliar esta questão, o composto 7,12 dimetilbenz[α]antraceneno, o qual é conhecido por induzir carcinogénese mamária em rato, foi administrado a ratos transgénicos que sobreepressam a RGN (Tg-RGN) e aos respetivos controlos (Wt, do inglês wild-type). Os ratos Tg-RGN apresentaram, notavelmente, uma menor incidência de tumores (25.8 %) comparativamente aos animais controlo (100 %). A classificação histológica também demonstrou uma clara resistência dos ratos Tg-RGN à tumorigénese, ao serem bastante mais resistentes à progressão dos tumores para estadios mais agressivos. Verificou-se uma muito menor percentagem de tumores do tipo invasivo nos animais transgénicos (3.8 % vs 45.8 % nos Wt). Para além disso, foi observado um aumento da atividade proliferativa nos tumores não-invasivos nos Wt comparativamente aos animais TG-RGN, o que indica a menor capacidade invasiva. A avaliação metabólica dos tumores benignos da glândula demonstrou que os tumores de ratos Tg-RGN possuem uma menor expressão e atividade da lactato desidrogenase (LDH), característica que normalmente se encontra associada a uma restrição da progressão tumoral e a um decréscimo da agressividade. Contudo, em tecido mamário não-neoplásico de ratos Tg-RGN observou-se uma restrição do metabolismo glicolítico, o que é indicativo de uma redução dos níveis energéticos no tecido. Estes resultados podem ser de extrema importância para a diminuição da proliferação celular e constituir um mecanismo adicional, pelo qual a RGN previne o desenvolvimento tumoral. De facto, a sobreexpressão da RGN originou uma diminuição da expressão de genes envolvidos na regulação ciclo celular e de oncogenes na glândula mamária de ratos…
Advisors/Committee Members: Socorro, Sílvia Cristina da Cruz Marques, Santos, Cecília Reis Alves.
Subjects/Keywords: Apoptose; Cancro da mama; Glândula mamária; Metabolismo glicolítico; Proliferação; Regucalcina; Tg-RGN; Apoptosis; Breast cancer; Glycolytic metabolism; Mammary gland; Proliferation; Regucalcin; Domínio/Área Científica::Ciências Médicas::Outras Ciências Médicas
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APA (6th Edition):
Marques, R. J. F. (2016). Biological evidence of the protective role of regucalcin in breast cancer. (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/4214
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marques, Ricardo Jorge Fernandes. “Biological evidence of the protective role of regucalcin in breast cancer.” 2016. Thesis, RCAAP. Accessed January 23, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/4214.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marques, Ricardo Jorge Fernandes. “Biological evidence of the protective role of regucalcin in breast cancer.” 2016. Web. 23 Jan 2021.
Vancouver:
Marques RJF. Biological evidence of the protective role of regucalcin in breast cancer. [Internet] [Thesis]. RCAAP; 2016. [cited 2021 Jan 23].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/4214.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marques RJF. Biological evidence of the protective role of regucalcin in breast cancer. [Thesis]. RCAAP; 2016. Available from: http://www.rcaap.pt/detail.jsp?id=oai:ubibliorum.ubi.pt:10400.6/4214
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
. 
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