Cooperation of V-oncogenes in human epithelial cell transformation.

The development of tissue culture systems for propagation of human epithelial cells has aided the investigation of events that lead epithelial cells to become neoplastic. In the present study, nontumorigenic human epidermal keratinocytes, immortalized by Ad12-SV40 virus or pSv3-neo, were transformed by a variety of retroviruses containing bas, H-ras, fes, fms, erbB and src oncogenes. Such transformants showed morphological alterations and induced carcinomas when transplanted into nude mice. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of Ad12-SV40 virus and retroviral oncogenes and support a multistep process for neoplastic conversion. This in vitro system may be useful in studying the interaction of a variety of retroviral oncogenes and human epithelial cells.