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Tumor Suppressor Genes and the Cellular Basis for Susceptibility to Breast Cancer

Reproductive factors and family history of breast cancer are the most important predictors of an individual’s risk of developing breast cancer. These observations emphasize the important contributions of both genetic background and hormonal exposures in determining breast cancer risk. Our laboratory has demonstrated an association between activity of the p53 tumor suppressor protein and incidence of mammary tumors. Expression and activity of p53 protein are responsive to hormonal stimuli and vary across different stages of mammary gland development. Therefore, a major focus of the laboratory is to discover the normal cellular mechanisms that regulate p53 function and determine whether sustained elevation in p53 activity prevents mammary tumors in response to physiologic stimuli. We also use genetic mapping strategies in mice to identify low-penetrance modifiers of mammary tumor susceptibility. Genes that regulate p53 function would provide novel targets for prevention and treatment of breast cancer. Through the use of contemporary techniques in molecular and cellular biology and animal models, we are defining the developmental biology of the breast epithelium itself, while identifying both the genetic and cellular basis for susceptibility to breast cancer.