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

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.

Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma

“…NCOA3 has been detected as being amplified in breast cancer (synonym AIB1). 26 It has also been described to be amplified in endometrial, stomach, prostate, pancreatic, and hepatocellular carcinomas. [27][28][29] NCOA3 is as transcription coactivator involved in cell proliferation, migration, differentiation, and growth.…”

Cofactor competition between the ligand-bound oestrogen receptor and an intron 1 enhancer leads to oestrogen repression of ERBB2 expression in breast cancer

“…Moreover both SRC-1 and TIF2, although widely expressed, have previously been identi®ed as competable, limiting factors particularly in the context of the squelching of progesterone receptor transactivation in the presence of ectopic ER expression (Onate et al, 1995;Voegel et al, 1996). Signi®cantly, both proteins are expressed at very modest levels in most breast tumour derived cell lines (Anzick et al, 1997;Berns et al, 1998) and levels of SRC-1 are also particularly low in patients who fail to respond to tamoxifen therapy (Berns et al, 1998).…”

“…The SRC-1 expression clones were in pSG5 and all based on the SRC-1e isoform and expressed at comparable levels (Kalkhoven et al, 1998;Bevan et al, 1999). AIB1 and TIF2 expression constructs have been described elsewhere (Anzick et al, 1997;Voegel et al, 1996). Cell monolayers were transiently transfected and subsequently hormonally manipulated as described previously (Bates and Hurst, 1997).…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…However, overexpression of AIB1, GRIP1, PELP1, MUC1, breast carcinoma amplified sequence 3 (BCAS3), Ciz1, SRA has been shown to induce breast carcinogenesis [172]. AIB1 and BCAS3 are both ERα coactivators known to be amplified, overexpressed, and associated with tamoxifen resistance in breast cancers [173,174]. A recent clinical study using 560 human breast tumor tissues found the AIB1 expression along with expression of genes involved in cell migration and invasion such as polyomavirus enhancer activator 3 and matrix metalloproteinases 2 and 9 suggesting a positive correlation of AIB1 expression with tumor metastasis [95].…”