Inhibition of c-erbB-2 oncogene expression by estrogens in human breast cancer cells.

The c-erbB-2 oncogene is thought to play a relevant role in the development and progression of mammary neoplasia. Using the human breast cancer cell lines T47D and MCF7, we found that the arrest of cell growth induced by a steroid-depleted medium was accompanied by a strong increase of c-erbB-2 mRNA and of the c-erbB-2-encoded p185 protein. The treatment of arrested cells with estrogens was found to resume cell proliferation and to inhibit dramatically c-erbB-2 expression at both mRNA and protein level. The regulation of c-erbB-2 expression was remarkably different from that observed for c-myc, which was strongly stimulated by estrogens, and ras, whose expression was unaffected all through the treatments. In addition, in the normal rat mammary gland undergoing development and differentiation during pregnancy and lactation, p185 expression was detected only in the functionally differentiated tissue. Altogether, our data indicate that the expression of c-erbB-2 is repressed during estrogen-induced proliferation and enhanced during growth arrest and/or differentiation of mammary cells.