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Title: The role of Rab35 in androgen sensitive ovarian cancer
Author: Hoo, San Soo
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2013
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Background Androgens have been implicated in high grade serous ovarian cancer. Rab35 has been shown to be upregulated following stimulation with androgens and there has been a positive correlation between the expression of Rab35 and androgen receptor (AR), suggesting that Rab35 may be an androgen regulated proto-oncogene, and a potential biomarker for anti-androgen therapy. Rab35 was validated as an androgen regulated gene and its functional effects in epithelial ovarian cancer investigated. Methods The upregulation of Rab35 expression in response to androgen stimulation was confirmed by Western blotting. Real-time PCRwas used to analyse Rab35 gene expression in OVCAR3 cells following dihydrotestosterone (OHT) stimulation with and without siRNA targeted against AR. Cell proliferation assays including S-phase analysis using flow cytometry and SRBassays were performed to examine the effect of Rab35 silencing on cell proliferation. Anti-active Caspase-3 analysis by flow cytometry and cleaved PARPexpression by Western blotting were used to investigate the effect of Rab35silencing on cell apoptosis. Results The upregulation of Rab35 gene expression was abrogated when AR was silenced. There was a decrease in the percentage of cells in S-phase and 20% to 3()o~decrease in cell proliferative index when Rab35 was silenced. There was an 11% to 24% increase in cell apoptosis upon silencing Rab35gene. Conclusions Overexpression of Rab35 has oncogenic effects in epithelial ovarian cancer causing an increase in cell proliferation and decrease in cell apoptosis. Tumour AR and Rab35 status may further refine patient selection for anti-androgen therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available