Interaction of AIB1 and BRCA1 in the Development of Breast Cancer

摘要

AIB1 (SRC3) belongs to the p160 family of steroid receptor coactivators including SRC-1 and SRC-2. AIB1 interacts with several nuclear receptors including estrogen and progesterone receptors in a ligand-dependent manner and enhances their transcriptional activity. AIB1 is amplified and overexpressed in >30% of breast cancers and can increase the sensitivity of breast cancer cells to estrogen and to growth factor signaling. BRCA1 regulates cell cycle progression, apoptosis induction, transcription, and DNA repair. From 5-10% of total breast cancers are due to germ-line BRCA1 mutations that lead to a deficiency in the BRCA1 protein. We have observed that AIB1 can partially reverse BRCA1 mediated repression of ERdependent transcriptional activity in breast cancer. This research will identify if there is a functional consequence of an interaction between AIB1 and BRCA1 in breast cancer.