Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells.
Somatic cell hybrids between MCF-7 human breast cancer cells and normal immortalized human mammary epithelial cells have been obtained by polyethylene glycol-mediated cell fusion. The hybrid cells are suppressed 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 angiogenesis 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 capabilities, and growth factor requirements.
Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, MA 02115.
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Zajchowski
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Band
D K
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Trask
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Kling
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Connolly
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Sager
D000818:Animals; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division; D002459:Cell Fusion; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology*; D007633:Keratins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D013370:Subrenal Capsule Assay; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology
D007633:Keratins