Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor.
In the present study, the role of BRCA1 in ligand-dependent androgen receptor (AR) signaling was assessed. In transfected prostate and breast cancer cell lines, BRCA1 enhanced AR-dependent transactivation of a probasin-derived reporter gene. The effects of BRCA1 were mediated through the NH2-terminal activation function (AF-1) of the receptor. Cotransfection of p160 coactivators markedly potentiated BRCA1-mediated enhancement of AR signaling. In addition, BRCA1 was shown to interact physically with both the AR and the p160 coactivator, glucocorticoid receptor interacting protein 1. These findings suggest that BRCA1 may directly modulate AR signaling and, therefore, may have implications regarding the proliferation of normal and malignant androgen-regulated tissues.
Park
J J
JJ
Breast Cancer Research Program of the University of Soulthern California/Norris Comprehensive Cancer Center, Los Angeles 90089-9176, USA.
Irvine
R A
RA
Buchanan
G
G
Koh
S S
SS
Park
J M
JM
Tilley
W D
WD
Stallcup
M R
MR
Press
M F
MF
Coetzee
G A
GA
D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics; D046508:Culture Techniques; D005260:Female; D015870:Gene Expression; D019398:Genes, BRCA1 / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051958:Nuclear Receptor Coactivator 2; D011099:Polyglutamic Acid / Q000494:pharmacology / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D014157:Transcription Factors; D011099:Polyglutamic Acid