Cancer Cells Hormone-dependent Regulation of BRCA1 in Human Breast

BRCA1 mRNA and protein levels are regulated by the steroid hor monesestrogenand progesteronein humanbreastcancercells. BRCA1 mRNA and protein levels were significantly decreased in estrogen-de pleted MCF-7 and BT2OT cells and increased again after stimulation with @3-estradiol. The increase in BRCA1 expression upon stimulation with estrogen was not coordinated with the early induction of the estrogen dependentpS2 gene but closely paralleledthe delayedincreasein the S-phase dependent marker cydlin 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 mdi racily by altering the proliferative status of the cells rather than acting directly on DNA sequences In the BRCA1 gene Itself.