Abstract:
Ovarian granulosa cell tumours (GCTs) are a specific subtype of malignant ovarian neoplasm which account for 5% of all ovarian cancers. GCTs are rare tumours which most commonly present in the early post-menopausal period. Although GCTs have a better short term prognosis than the more common epithelial ovarian carcinomas, in the longer term approximately 50% of patients will have tumour recurrence and 80% of these patients will die from their disease. Currently women with ovarian GCTs receive similar treatment as those with epithelial ovarian cancer, but given the unique biology of granulosa cells, GCTs are likely to respond differently to the more common epithelial ovarian tumours. Alternative GCT-specific treatments and prognostic markers are needed if outcomes are to be improved. The aim of this thesis was to characterise the role of oestrogen receptor ß (ERß) in ovarian granulosa cell tumours, in order to determine its potential as a GCT-specific prognostic marker and treatment target. Specific objectives were: to investigate the hypothesis that ERß inhibits cell proliferation in the ovarian GCT-derived cell lines COV434 and KGN-T, and to determine what genes and gene pathways are uniquely expressed in ovarian granulosa cell tumours compared to other ovarian cancers. ERß has been identified as a potential tumour suppressor in many human malignancies, and its effect on proliferation in two GCT-derived cell lines was studied with the aid of an ERß-specific agonist, diarylpropionitrile (DPN), and by silencing expression of ERß using small interfering RNAs (siRNA). Treatment of the GCTderived cell lines with DPN inhibited growth, and silencing expression of ERß with siRNA resulted in a significant increase in cell proliferation.
