Cooperative transforming activities of ras, myc, and src viral oncogenes in nonestablished rat adrenocortical cells.
Early-passage rat adrenocortical cells were infected with Kirsten murine sarcoma virus and MMCV mouse myc virus, two retroviruses carrying the v-Ki-ras and v-myc oncogenes, respectively. Efficient morphological transformation required coinfection with the two viruses, was dependent on the presence of high serum concentrations, and was not immediately accompanied by growth in soft agar. The doubly infected cells coordinately acquired the capacity for anchorage- and serum-independent growth during passage in culture. The appearance of such highly transformed cells was correlated with the emergence of a dominant clone, as suggested by an analysis of retrovirus integration sites. These results indicate that the concerted expression of v-Ki-ras and v-myc could induce rapid morphological transformation of nonestablished adrenocortical cells but that an additional genetic or epigenetic event was required to permit full transformation by these two oncogenes. In contrast, v-src, introduced by retrovirus infection in conjunction with v-myc, rapidly induced serum- and anchorage-independent growth. Therefore, the p60v-src protein-tyrosine kinase, unlike p21v-ras, is apparently not restricted in the induction of a highly transformed phenotype in adrenocortical cells. This system provides an in vitro model for the progressive transformation of epithelial cells by dominantly acting oncogenes.
MacAuley
A
A
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Pawson
T
T
D000302:Adrenal Cortex / Q000166:cytology / Q000382:microbiology*; D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D015247:Deoxyribonuclease HindIII; D005786:Gene Expression Regulation; D011905:Genes, ras; D007708:Kirsten murine sarcoma virus / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D016274:Oncogene Protein p55(v-myc); D015688:Oncogene Protein pp60(v-src); D009857:Oncogenes; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D051381:Rats; D012191:Retroviridae Proteins / Q000235:genetics
D016274:Oncogene Protein p55(v-myc); D012191:Retroviridae Proteins; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D015247:Deoxyribonuclease HindIII