Neoplastic transformation of a human bronchial epithelial cell line by a recombinant retrovirus encoding viral Harvey ras.
Activated ras oncogenes have previously been implicated in the pathogenesis of human lung carcinomas. A v-Ha-ras-containing retrovirus, Zip-ras, was generated by inserting the coding region of the v-Ha-ras oncogene into the Zip-NeoSV(X) [Cepko et al., Cell 37:1053-1062, 1984] retroviral vector. Amphotrophic Zip-ras retrovirus was used to infect an SV40 large T antigen-positive immortalized cell line, BEAS-2B, derived from normal bronchial epithelial cells, the predominant progenitor cells of human lung carcinomas. Zip-ras-infected BEAS-2B cells selected for G418 resistance formed anaplastic carcinomas in 12 of 15 athymic nude mice (latency 3 wk), whereas Zip-NeoSV(X)-infected BEAS-2B control cultures inoculated into 12 nude mice formed no tumors after a minimum of 7 mo. Tumor cell lines were established and demonstrated to be of human epithelial origin and to express v-Ha-ras p21 protein. A common feature of the tumor cell lines was an increase in ploidy. The increased efficiency of neoplastic transformation by v-Ha-ras of cell lines as compared with our previous results with normal bronchial epithelial cells [Yoakum et al., Science 227:1174-1179, 1985] is consistent with the hypothesis that the "immortalization" step is rate-limiting in in vitro human epithelial cell carcinogenesis.
Amstad
P
P
Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.
Reddel
R R
RR
Pfeifer
A
A
Malan-Shibley
L
L
Mark
G E
GE
Harris
C C
CC
D000818:Animals; D001980:Bronchi / Q000166:cytology*; D001984:Bronchial Neoplasms / Q000473:pathology; D015197:Carcinogenicity Tests; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral; D004847:Epithelial Cells; D011905:Genes, ras; D006801:Humans; D007527:Isoenzymes; D051379:Mice; D008819:Mice, Nude; D011995:Recombination, Genetic; D013539:Simian virus 40 / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000473:pathology
D007527:Isoenzymes