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Scientist: Child Health Research Institute, London Health Sciences Centre, London, Ontario
Assistant Professor: Department of Biochemistry, University of Western Ontario, London, Ontario
Cancer Research Laboratory Program
London Regional Cancer Program, London Health Sciences Centre
Victoria Research Labs, Room A4-144
Canada N6A 4L6
Tel: 519.685.8600 Ext. 55988
In humans and other mammals, estrogens act on their target cells by binding to and activating the estrogen receptor (ER), a ligand-activated transcription factor that regulates the expression of estrogen-responsive genes. Two forms of the ER have been identified, ER and ER. My overall research goal is to understand ER’s molecular mechanism of action and its role in cellular proliferation, atresia (apoptosis) and differentiation.
Ovarian cancer is the fifth cause of cancer-related death in Canadian women. In the ovary, the oocyte is surround by granulosa cells, which contain ERbut very little ERGranulosa cell tumours (GCTs) account for five percent of ovarian tumours, but the molecular basis of GCT is unclear. GCTS, like normal granulosa cells, produce and respond to estradiol, and express high levels of ER. In the normal growing follicle, estrogens protect the follicle and its constituent cells from atresia (apoptosis), a process which requires estrogen, possibly acting through ER. Estrogen also regulates follicle stimulating hormone (FSH)-induced granulosa cell proliferation, differentiation, and cell-cell contacts, and my current work suggests that ER plays a role in these responses. The most active phase of granulosa cell proliferation is during the preantral to preovulatory transition, which is triggered by FSH. Interestingly, the molecular phenotype of GCTs most resembles granulosa cells of a preovulatory follicle (one stimulated with FSH), and it is this response to FSH that ER-null granulosa cells are lacking. Therefore, elucidation of the molecular function of ER in granulosa cells at this stage may lead to a better understanding of the aetiology of GCTs, and other tumours derived from estrogen-responsive tissues which express ER almost exclusively, such as prostate and colon. In breast tumours, in which estrogen is a mitogen and in which ER and ER are coexpressed, ERis thought to protect against estrogen-stimulated proliferation driven through ER. Understanding how ERcarries out this protective function may lead to development of novel pharmacological agents that enhance this protective effect.