Hormone-dependent regulation of BRCA1 in human breast cancer cells.
BRCA1 mRNA and protein levels are regulated by the steroid hormones estrogen and progesterone in human breast cancer cells. BRCA1 mRNA and protein levels were significantly decreased in estrogen-depleted MCF-7 and BT20T cells and increased again after stimulation with beta-estradiol. The increase in BRCA1 expression upon stimulation with estrogen was not coordinated with the early induction of the estrogen-dependent pS2 gene but closely paralleled the delayed increase in the S-phase dependent marker cyclin A. T47-D cells deprived of steroid hormones and subsequently stimulated with progesterone also showed a delayed increase in BRCA1 mRNA expression. However, no change in BRCA1 protein was detected in these cells. When considered together, the data suggest that steroid hormones may affect BRCA1 expression indirectly by altering the proliferative status of the cells rather than acting directly on DNA sequences in the BRCA1 gene itself.
Gudas
J M
JM
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Nguyen
H
H
Li
T
T
Cowan
K H
KH
D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D016213:Cyclins / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009363:Neoplasm Proteins / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011506:Proteins; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D019313:BRCA1 Protein; D016213:Cyclins; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D014157:Transcription Factors; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D011374:Progesterone; D004958:Estradiol