AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer

S L Anzick; J Kononen; R L Walker; D O Azorsa; M M Tanner; X Y Guan; G Sauter; O P Kallioniemi; J M Trent; P S Meltzer

doi:10.1126/science.277.5328.965

AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer

Science. 1997 Aug 15;277(5328):965-8. doi: 10.1126/science.277.5328.965.

Authors

S L Anzick¹, J Kononen, R L Walker, D O Azorsa, M M Tanner, X Y Guan, G Sauter, O P Kallioniemi, J M Trent, P S Meltzer

Affiliation

¹ Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

PMID: 9252329
DOI: 10.1126/science.277.5328.965

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.

MeSH terms

Amino Acid Sequence
Breast / metabolism
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Chromosomes, Human, Pair 20
Cloning, Molecular
Estradiol / metabolism
Estradiol / pharmacology
Female
Gene Amplification*
Gene Dosage
Gene Expression Regulation, Neoplastic
Histone Acetyltransferases
Humans
In Situ Hybridization, Fluorescence
Ligands
Molecular Sequence Data
Neoplasms, Hormone-Dependent / genetics*
Neoplasms, Hormone-Dependent / metabolism
Nuclear Receptor Coactivator 1
Nuclear Receptor Coactivator 2
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism
Receptors, Estrogen / genetics
Receptors, Estrogen / metabolism*
Transcription Factors / genetics
Transcriptional Activation
Transfection
Tumor Cells, Cultured

Substances

Ligands
Nuclear Receptor Coactivator 2
Receptors, Estrogen
Transcription Factors
Estradiol
Histone Acetyltransferases
NCOA1 protein, human
Nuclear Receptor Coactivator 1

Associated data

GENBANK/AF012108
GENBANK/U59302
GENBANK/X97674