The Estrogen Receptor and Its Variants as Risk Factors in Breast Cancer

The overall goal of this research is to understand how the estrogen receptor ER signal transduction pathway is altered during breast tumorigenesis and if altered ER signal transduction increases the risk of developing breast cancer. Our previous data suggest that altered expression of ER-Alpha ER-Beta and their variants occurs during breast tumorigenesis. Our current data suggest that at least two co-activators of ER, i.e., SPA and AIE1, as well as activated MAP kinase, that can activate ER in a ligand independent fashion, are significantly increased during breast tumorigenesis. In contrast, a repressor of ER activity REA is not significantly altered during breast tumorigenesis. Our previous results together with our current results suggest that multiple factors involved in estrogen receptor mediated signal transduction, are altered during human breast tumorigenesis and may have a role in the development of breast cancer. These data are consistent with the hypothesis that alterations of ER signal transduction occurring during the early stages of pre-neoplastic progression may effect the risk of developing breast cancer.