SV40-INDUCED IMMORTALIZATION AND RAS-TRANSFORMATION OF HUMAN BRONCHIAL EPITHELIAL-CELLS

Non-tumorigenic SV40-immortalized human cells may be transformed to tu morigenicity by activated oncogenes, but the molecular genetics of thi s process are still poorly understood. We describe here 4 SV40-transfo rmed bronchial epithelial (BE) cell lines that became immortalized aft er a period of crisis, and then transfection of 6 BE lines or sub-line s with an activated c-Ha-ras (EJ-ras) oncogene. pSV(2)neo-transfected cells did not form any tumors in athymic nude mice. Even though each o f the EJ-ras-transfected lines was shown to be expressing the mutant r os gene, only one cell line, BEAS-2B, and 2 of its sub-lines were tumo rigenic after transfection. We conclude that immortalization is not su fficient for BE cells to be transformed by the EJ-ras oncogene. Thus t here ave at least 2 unknown genetic events in this in vitro model of c arcinogenesis: escape from crisis (immortalization), and development o f ability to cooperate with activated ras in tumorigenic transformatio n. We found no evidence that either immortalization or ability to comp lement ros is related to abnormalities of the SV40 T antigens, of p110 (RB) Or Of p53. (C) 1995 Wiley-Liss, Inc.