Effect of \-rasH Oncogene Transfection on Estrogen-independent Tumorigenicity of Estrogen-dependent Human Breast Cancer Cells

Spontaneous or therapeutic-ally induced progression of hormone-de pendent human breast cancer to a form not amenable to endocrine treatment has been frequently recorded in clinical settings. In an experi mental 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, y-ras", into this cell line by means of DNA transaction. We now show that the oncogene-transfected hormone-independent MCF-7 cells may secrete diffusible tumorigenie factors that not only support their own tumor growth in vivo, but are also Immorally 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 condi tioned media from MCF-7-roi 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 5to 7-fold enhancement in anchorageindependent growth of MCF-7 cells was observed in the presence of MCF-7-raÃfeeder cell layer. These data suggest that v-r<w"-induced estrogen-independent tumorigenicity of human breast cancer cells occurs by secretion of mitogens which may function in an endocrine manner.