NEOPLASTIC TRANSFORMATION OF A HUMAN BRONCHIAL EPITHELIAL-CELL LINE BY A RECOMBINANT RETROVIRUS ENCODING VIRAL HARVEY RAS
NEOPLASTIC TRANSFORMATION OF A HUMAN BRONCHIAL EPITHELIAL-CELL LINE BY A RECOMBINANT RETROVIRUS ENCODING VIRAL HARVEY RAS
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DOI：
10.1002/mc.2940010303
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发表时间：
1988-01-01
影响因子：
4.6
通讯作者：
HARRIS, CC
中科院分区：
文献类型：
--
作者：
AMSTAD, P;REDDEL, RR;HARRIS, CC
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. 19841 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, 19851 is consistent with the hypothesis that the" immortalization" step is rate-limiting in in vitro human epithelial cell carcinogenesis.
