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Androgen-related expression of G-proteins in ovarian cancer

Lookup NU author(s): Dr Ali Kucukmetin, Sarah Wilkinson, Dr Ann Fisher, Dr Ahmed Elattar, Professor Craig Robson, Professor Richard Edmondson

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Abstract

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. British Journal of Cancer (2009) 101, 498-503. doi:10.1038/sj.bjc.6605153 www.bjcancer.com Published online 21 July 2009 (C) 2009 Cancer Research UK


Publication metadata

Author(s): Sheach LA, Adeney EM, Kucukmetin A, Wilkinson SJ, Fisher AD, Elattar A, Robson CN, Edmondson RJ

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2009

Volume: 101

Issue: 3

Pages: 498-503

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.bjc.6605153

DOI: 10.1038/sj.bjc.6605153


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