AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.
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.
Anzick
S L
SL
Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Kononen
J
J
Walker
R L
RL
Azorsa
D O
DO
Tanner
M M
MM
Guan
X Y
XY
Sauter
G
G
Kallioniemi
O P
OP
Trent
J M
JM
Meltzer
P S
PS
D000595:Amino Acid Sequence; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002890:Chromosomes, Human, Pair 20; D003001:Cloning, Molecular; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008024:Ligands; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D008024:Ligands; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D014157:Transcription Factors; D004958:Estradiol; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1