HORMONE-DEPENDENT REGULATION OF BRCA1 IN HUMAN BREAST-CANCER CELLS

BRCA1 mRNA and protein levels are regulated by the steroid hormones es trogen and progesterone in human breast cancer cells, BRCA1 mRNA and p rotein levels were significantly decreased in estrogen-depleted MCF-7 and BT20T cells and increased again after stimulation with beta-estrad iol, The increase in BRCA1 expression upon stimulation with estrogen w as not coordinated with the early induction of the estrogen-dependent pS2 gene but closely paralleled the delayed increase in the S-phase de pendent marker cyclin A. T47-D cells deprived of steroid hormones and subsequently stimulated with progesterone also showed a delayed increa se in BRCA1 mRNA expression, However, no change in BRCA1 protein was d etected in these cells, When considered together, the data suggest tha t steroid hormones may affect BRCA1 expression indirectly by altering the proliferative status of the cells rather than acting directly on D NA sequences in the BRCA1 gene itself.