AIB1 enhances estrogen-dependent induction of cyclin D1 expression

AIB1 was isolated as a gene amplified in breast cancer and encodes a protei n that acts as a steroid receptor coactivator, The role of steroid receptor coactivators such as AIB1 in breast cancer development is not clear. It is possible that AIB1 cooperates with estrogen receptor a in regulating estro gen-dependent cell proliferation. Ectopic expression of the estrogen recept or a in different cell lines does not confer estrogen-induced proliferation , This inability of the estrogen receptor to drive proliferation has been r ecently correlated with a lack of estrogen-dependent cyclin D1 expression i n cells engineered to express the estrogen receptor. In this study, we eval uated whether high levels of AIB1 enable the estrogen receptor to direct th e transcription of cyclin D1, We show here that AIB1 and other steroid rece ptor coactivators can enhance the functional interaction of the estrogen re ceptor with the cyclin D1 promoter. Increases of AIB1 levels in breast canc er cells by amplification and/or overexpression may represent one way to co nfer estrogen-dependent mitogenic stimulation to breast cancer cells.