Transfection of v-rasH DNA 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-rasH onc gene was transfected into MCF-7 cells. The cloned MCF-7ras transfectants, which expressed the v-rasH messenger RNA and v-rasH p21 protein (21,000 daltons), were characterized. In contrast to the parental cell line, MCF-7ras 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-7ras cells were fully tumorigenic in the absence of estrogen supplementation. Thus, cells acquiring an activated onc gene can bypass the hormonal regulatory signals that trigger the neoplastic growth of a human breast cancer cell line.
D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D004273:DNA, Neoplasm / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics; D009857:Oncogenes; D011759:Pyrrolidines / Q000494:pharmacology; D012091:Repetitive Sequences, Nucleic Acid; D013876:Thiophenes / Q000494:pharmacology; D014162:Transfection
D004273:DNA, Neoplasm; D004967:Estrogens; D011759:Pyrrolidines; D013876:Thiophenes; C025430:LY 117018