Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells (tumor suppression/somatic cell hybrids/keratins/thrombospondin/flbronectin)

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Somatic cell hybrids between MCF-7 human breast cancer cells and immortalized human mammary epithelial cells have been obtained by polyethylene glycol- mediated cell fusion. The hybrid cells are in their ability to form tumors in nude mice, as well as in traits specific to the tumorigenic MCF-7 parent: growth factor independence, tumor necrosis factor sensitivity, and pS2 gene expression. In addition, they display other characteristics of the normal parent, including increased expression relative to the MCF-7 cells of the genes for the extracellular matrix component fibronectin, the intermediate filament keratin 5, and the an- giogenesis inhibitor thrombospondin. The levels of keratins 8 and 18 also resemble those of the nontumorigenic parent. These results provide evidence for the existence of tumor suppressor gene products in immortal mammary epithelial cells. We propose a characteristic suppressed tumor cell phenotype, which encompasses altered cytoarchitecture, angiogenesis ca- pabilities, and growth factor requirements.

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