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.