[Truncated abstract] Ovarian cancer is currently the leading cause of death from gynaecological malignancies in women from developed countries. Serous ovarian cancer is the most prevalent type of all ovarian cancers, with the majority diagnosed in an advanced stage where treatment efficacy is reduced and patient survival is poor. Because of this fact, the development of improved detection and treatment strategies are necessary, with much research focussing on the complex molecular pathways involved in ovarian tumour growth as one potential avenue for intervention. Apoptosis, or programmed cell death, is one such area of investigation because currently successful cancer treatments induce apoptosis in tumour cells. Molecular analysis of apoptosis in both normal tissue and tumours has established a positive relationship between increased expression of secreted frizzled-related protein 4 (SFRP4) and apoptosis, however to date, very little research has focussed on the role of this gene in the ovary . . . An examination of SFRP4 and β-catenin expression in 163 primary serous ovarian carcinomas revealed high SFRP4 expression was associated with low β-catenin expression and conversely, low SFRP4 was associated with high β-catenin expression in the majority of the ovarian tumours analysed, reinforcing the inverse relationship observed in the ovarian cell lines. A positive trend was observed between cancer stage and the expression level of these proteins, with increased SFRP4 expression and reduced β-catenin expression as cancer stage increased. Additionally, patient survival revealed a trend towards increased survival among ovarian cancer patients who had tumours expressing low levels of SFRP4. Taken together, the novel findings of this study indicate that the increased expression of SFRP4 observed in a large proportion of serous ovarian cancers is a cellular response to down-regulate the level of β-catenin, and thus an attempt to maintain cellular homeostasis by counteracting the excessive proliferating signals present in these tumour cells.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2006|