AIB1, a Steroid Receptor Coactivator Amplified in Breast and Ovarian Cancer

TLDR

The SRC‑1 family of transcriptional coactivators enhances ligand‑dependent transcription by interacting with steroid hormone receptors. AIB1 was identified on chromosome 20 as a gene with elevated expression and copy number in breast cancers, and its protein interacts with estrogen receptors in a ligand‑dependent manner, enhancing estrogen‑dependent transcription when overexpressed. AIB1 amplification occurs in ~10 % of primary breast cancers and in most estrogen‑receptor‑positive breast and ovarian cancer cell lines, with high expression in 64 % of tumors, indicating that its altered expression may drive steroid‑dependent cancer development.

Abstract

Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in human breast cancers. AIB1 amplification and overexpression were observed in four of five estrogen receptor-positive breast and ovarian cancer cell lines. Subsequent evaluation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 percent of the primary tumors analyzed. AIB1 protein interacted with estrogen receptors in a ligand-dependent fashion, and transfection of AIB1 resulted in enhancement of estrogen-dependent transcription. These observations identify AIB1 as a nuclear receptor coactivator whose altered expression may contribute to development of steroid-dependent cancers.