Grant: Operating Grant

The majority of ovarian cancers arise from epithelial cells in the ovary, but the cellular and molecular events associated with early development of ovarian cancer are poorly understood. Epidemiologic studies have identified a number of reproductive factors that increase the risk of ovarian cancer, such as ovulation and certain hormones, notably estrogen. In addition, hereditary risk (family history) is associated with the more frequent incidence of pre- cancerous structures in the ovary. The mechanisms by which these factors increase the risk of ovarian cancer are unknown. The goal of this project is to address how ovarian cancers begin, with particular emphasis on reproductive factors, notably estrogen, that have been implicated in the initiation or progression of ovarian cancer. We hypothesize that these factors may promote the development of ovarian cancer by manipulating the behaviour of the epithelial cells of the ovary. The experimental strategies described in this proposal focus on a recently developed transgenic model of ovarian cancer that enables us to monitor tumour initiation and progression in a manner that is not possible in humans. We have shown that this model develops pre-cancerous changes and tumour responses that indicate its relevance to human ovarian cancer. The results of these experiments will significantly advance our knowledge about the origins of ovarian cancer, and have the potential to reveal possible explanations for the epidemiological studies that have linked ovulation and estrogen therapy to increased ovarian cancer risk. Perhaps more importantly, this study may identify processes or interventions that are protective against the initiation and/or progression of ovarian cancer leading to new strategies for disease prevention.