Transfection of v-ras^HDNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity

The natural history of estrogen-responsive breast cancers often involves a phenotypic change to an estrogen-unresponsive, more aggressive tumor. The human breast cancer cell line, MCF-7, which requires estradiol for tumor formation in vivo and shows growth stimulation in response to estradiol in vitro, is a model for hormone-responsive tumors. The v-ras^H onc gene was transfected into MCF-7 cells. The cloned MCF-7_ras transfectants, which expressed the v-ras^H messenger RNA and v-ras^H p21 protein (21,000 daltons), were characterized. In contrast to the parental cell line, MCF-7 _ras cells no longer responded to exogenous estrogen in culture and their growth was minimally inhibited by exogenous antiestrogens. When tested in the nude mouse, the MCF-7_ras cells were fully tumorigenic in the absence of estrogen supplementation. Thus, cells acquiring an activated one gene can bypass the hormonal regulatory signals that trigger the neoplastic growth of a human breast cancer cell line.