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Androgen-related expression of G-proteins in ovarian cancer

BACKGROUND: Epidemiological and in vitro data implicate androgens in the aetiology of ovarian cancer, but the mechanisms by which this is mediated are unclear. In this study, we wished to examine the effects of androgens on gene expression in ovarian cancer. METHODS: The expression of androgen recep...

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Autores principales: Sheach, L A, Adeney, E M, Kucukmetin, A, Wilkinson, S J, Fisher, A D, Elattar, A, Robson, C N, Edmondson, R J
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720237/
https://www.ncbi.nlm.nih.gov/pubmed/19623182
http://dx.doi.org/10.1038/sj.bjc.6605153
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author Sheach, L A
Adeney, E M
Kucukmetin, A
Wilkinson, S J
Fisher, A D
Elattar, A
Robson, C N
Edmondson, R J
author_facet Sheach, L A
Adeney, E M
Kucukmetin, A
Wilkinson, S J
Fisher, A D
Elattar, A
Robson, C N
Edmondson, R J
author_sort Sheach, L A
collection PubMed
description BACKGROUND: Epidemiological and in vitro data implicate androgens in the aetiology of ovarian cancer, but the mechanisms by which this is mediated are unclear. In this study, we wished to examine the effects of androgens on gene expression in ovarian cancer. METHODS: The expression of androgen receptor (AR) in OVCAR3 and OSEC2 cells was confirmed using immunoblotting and response to androgens was measured using flow cytometric assessment of S-phase fraction. The differential gene expression between androgen stimulated and unstimulated OVCAR3 ovarian cancer cells was examined with a cDNA microarray. The upregulation of a subset of these genes was then confirmed with reverse transcriptase PCR in both OVCAR3 and OSEC2, an ovarian epithelial cell line. Finally, the clinical significance of this upregulation was investigated by examining the expression of Rab25 and Rab35, two G-protein-related molecules in an ovarian cancer tissue microarray (TMA). RESULTS: OVCAR3 and OSEC2 cells were shown to express the AR and showed an increase in S-phase fraction in response to androgen treatment. Treatment of OVCAR3 cells with androgen resulted in a significant upregulation of 121 genes. These findings were confirmed for a subset of seven monomeric G-protein-related genes in both OVCAR3 and OSEC2 cells. After staining for Rab25 and Rab35, the majority of TMA sections examined showed expression for Rab25 (92%) and Rab35 (95%). The expression of Rab25 correlated with histological grade, and expression was higher in endometrioid (median histoscore 10.5) than serous (7.5) or mucinous (5.3) tumours. The expression of Rab25 correlated positively with AR expression supporting its role as an androgen responsive gene in ovarian cancer. CONCLUSIONS: These results suggest that androgens can effect expression of the oncogenic GTPases in ovarian cancer. We propose that the androgen responsive Rab35 may have clinical importance as a biomarker of AR function.
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spelling pubmed-27202372010-08-04 Androgen-related expression of G-proteins in ovarian cancer Sheach, L A Adeney, E M Kucukmetin, A Wilkinson, S J Fisher, A D Elattar, A Robson, C N Edmondson, R J Br J Cancer Molecular Diagnostics BACKGROUND: Epidemiological and in vitro data implicate androgens in the aetiology of ovarian cancer, but the mechanisms by which this is mediated are unclear. In this study, we wished to examine the effects of androgens on gene expression in ovarian cancer. METHODS: The expression of androgen receptor (AR) in OVCAR3 and OSEC2 cells was confirmed using immunoblotting and response to androgens was measured using flow cytometric assessment of S-phase fraction. The differential gene expression between androgen stimulated and unstimulated OVCAR3 ovarian cancer cells was examined with a cDNA microarray. The upregulation of a subset of these genes was then confirmed with reverse transcriptase PCR in both OVCAR3 and OSEC2, an ovarian epithelial cell line. Finally, the clinical significance of this upregulation was investigated by examining the expression of Rab25 and Rab35, two G-protein-related molecules in an ovarian cancer tissue microarray (TMA). RESULTS: OVCAR3 and OSEC2 cells were shown to express the AR and showed an increase in S-phase fraction in response to androgen treatment. Treatment of OVCAR3 cells with androgen resulted in a significant upregulation of 121 genes. These findings were confirmed for a subset of seven monomeric G-protein-related genes in both OVCAR3 and OSEC2 cells. After staining for Rab25 and Rab35, the majority of TMA sections examined showed expression for Rab25 (92%) and Rab35 (95%). The expression of Rab25 correlated with histological grade, and expression was higher in endometrioid (median histoscore 10.5) than serous (7.5) or mucinous (5.3) tumours. The expression of Rab25 correlated positively with AR expression supporting its role as an androgen responsive gene in ovarian cancer. CONCLUSIONS: These results suggest that androgens can effect expression of the oncogenic GTPases in ovarian cancer. We propose that the androgen responsive Rab35 may have clinical importance as a biomarker of AR function. Nature Publishing Group 2009-08-04 2009-07-21 /pmc/articles/PMC2720237/ /pubmed/19623182 http://dx.doi.org/10.1038/sj.bjc.6605153 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Sheach, L A
Adeney, E M
Kucukmetin, A
Wilkinson, S J
Fisher, A D
Elattar, A
Robson, C N
Edmondson, R J
Androgen-related expression of G-proteins in ovarian cancer
title Androgen-related expression of G-proteins in ovarian cancer
title_full Androgen-related expression of G-proteins in ovarian cancer
title_fullStr Androgen-related expression of G-proteins in ovarian cancer
title_full_unstemmed Androgen-related expression of G-proteins in ovarian cancer
title_short Androgen-related expression of G-proteins in ovarian cancer
title_sort androgen-related expression of g-proteins in ovarian cancer
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720237/
https://www.ncbi.nlm.nih.gov/pubmed/19623182
http://dx.doi.org/10.1038/sj.bjc.6605153
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