Regulation and Role of Nuclear Receptor Coactivator AIB1 in Breast Cancer

摘要

AIB1 (Amplified in Breast Cancer 1) is a nuclear receptor coactivator found amplified and overexpressed in a subset of breast cancers. AIB1 potentiates the transcriptional activity of the estrogen, progesterone, thyroid hormone, and retinoid receptors. It is necessary for normal female reproductive function and mammary gland development and is rate-limiting for tumor growth in nude mice. It is hypothesized that the amplification and Overexpression of AIB1 contribute to the promotion and/or progression of breast cancer. An understanding of the regulation of expression of AIB1 will give insight into the role of AIBl in breast cancer. This work has shown that antiestrogens, retinoids, and TGF-Th contribute to the overexpression of AIB1 in MCF-7 breast cancer cells. The putative promoter for the AIB1 gene has been identified. Regulatory elements involved in the regulation of AIB1 by antiestrogens, retinoids, and TGF-beta were not found in the cloned promoter regions and may be upstream or intronic enhancer elements. Further studies will explore the consequences of overexpression of AIBl through stable transfection in to a cell line with low endogenous levels of AIB1.