BRCA1 inhibition of estrogen receptor signaling in transfected cells.
Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.
Fan
S
S
Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, 270-05 76th Avenue, New Hyde Park, NY 11040, USA.
Wang
J
J
Yuan
R
R
Ma
Y
Y
Meng
Q
Q
Erdos
M R
MR
Pestell
R G
RG
Yuan
F
F
Auborn
K J
KJ
Goldberg
I D
ID
Rosen
E M
EM
D019313:BRCA1 Protein / Q000502:physiology*; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000209:etiology; D002455:Cell Division; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells / Q000166:cytology; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D019398:Genes, BRCA1; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D008297:Male; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D047628:Estrogen Receptor alpha; D008024:Ligands; D011960:Receptors, Estrogen; D014157:Transcription Factors; D004958:Estradiol