Rr. Reddel et al., SV40-INDUCED IMMORTALIZATION AND RAS-TRANSFORMATION OF HUMAN BRONCHIAL EPITHELIAL-CELLS, International journal of cancer, 61(2), 1995, pp. 199-205
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.