Effect of v-rasH oncogene transfection on estrogen-independent tumorigenicity of estrogen-dependent human breast cancer cells.
Spontaneous or therapeutically induced progression of hormone-dependent human breast cancer to a form not amenable to endocrine treatment has been frequently recorded in clinical settings. In an experimental model system, we have changed the estrogen-dependent tumorigenicity of a human breast cancer cell line, MCF-7, to an independent state by stably introducing a model oncogene, v-rasH, into this cell line by means of DNA transfection. We now show that the oncogene-transfected hormone-independent MCF-7 cells may secrete diffusible tumorigenic factors that not only support their own tumor growth in vivo, but are also humorally active in partially triggering the tumor growth of wild type previously nontumorigenic MCF-7 cells, even when the wild type cells are implanted at a distant anatomical site in the same animal. Estrogen-independent tumor formation by MCF-7 cells was also induced in 50% of animals given injection by continuous administration of conditioned media from MCF-7-ras cells. However, the wild type tumors had limited tumor growth. Tumors were verified as adenocarcinomas and by Southern blotting were shown to be derived from the cells injected. In an in vitro coculture assay, a 5- to 7-fold enhancement in anchorage-independent growth of MCF-7 cells was observed in the presence of MCF-7-ras feeder cell layer. These data suggest that v-rasH-induced estrogen-independent tumorigenicity of human breast cancer cells occurs by secretion of mitogens which may function in an endocrine manner.
Kasid
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Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892.
Knabbe
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C
Lippman
M E
ME
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D004273:DNA, Neoplasm / Q000032:analysis; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D009857:Oncogenes; D014162:Transfection; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004273:DNA, Neoplasm; D004967:Estrogens