Browse by author
Lookup NU author(s): Dr Ali Kucukmetin, Sarah Wilkinson, Dr Ann Fisher, Dr Ahmed Elattar, Professor Craig Robson, Professor Richard Edmondson
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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
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
Altmetrics provided by Altmetric
