AIB1, A STEROID-RECEPTOR COACTIVATOR AMPLIFIED IN BREAST AND OVARIAN-CANCER

Members of the recently recognized SRC-1 family of transcriptional coa ctivators interact with steroid hormone receptors to enhance ligand-de pendent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expre ssion and copy number were elevated in human breast cancers. AIB1 ampl ification and overexpression were observed in four of five estrogen re ceptor-positive breast and ovarian cancer cell lines. Subsequent evalu ation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 pe rcent of the primary tumors analyzed. AIB1 protein interacted with est rogen receptors in a ligand-dependent fashion, and transfection of AIB 1 resulted in enhancement of estrogen-dependent transcription, These o bservations identify AIB1 as a nuclear receptor coactivator whose alte red expression may contribute to development of steroid-dependent canc ers.