Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: altered response to inducers of terminal squamous differentiation.
Many human bronchial adenocarcinomas have been shown to contain an activated Ki-ras oncogene (Rodenhuis et al., N. Engl. J. Med. 317 929-935, 1987). To test the hypothesis that activated Ki-ras may be causally related to human bronchial carcinogenesis, v-Ki-ras oncogene was transferred into an established human bronchial epithelial cell line, BEAS-2B, by infection with Kirsten murine sarcoma virus (Ki-MSV) or by transfection with a plasmid containing the transforming region of Ki-MSV. These cells formed poorly differentiated adenocarcinomas in athymic nude mice. Cell lines established from these tumors expressed v-Ki-ras p21 protein and were highly tumorigenic. Whereas serum or transforming growth factor beta 1 induced the BEAS-2B cells at clonal density to undergo growth arrest and squamous differentiation, BEAS-2B cells containing activated ras genes were unaffected by transforming growth factor beta 1 and were mitogenically stimulated by serum.
Reddel
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Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Ke
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Kaighn
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Malan-Shibley
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Lechner
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Rhim
J S
JS
Harris
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D000818:Animals; D001980:Bronchi / Q000166:cytology*; D001984:Bronchial Neoplasms / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D011905:Genes, ras; D006133:Growth Substances / Q000097:blood; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D015291:Transforming Growth Factors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D015291:Transforming Growth Factors