Expression of Kirsten murine sarcoma virus in transformed nonproducer and revertant NIH/3T3 cells: evidence for cell-mediated resistance to a viral oncogene in phenotypic reversion.

Expression of the provirus in a clonally related series of Kirsten murine sarcoma virus-transformed NIH/3T3 nonproducer cell lines was examined at both the transcriptional and translational levels. All cells expressed high levels of genome-sized viral RNA with little variation between cell lines despite differences in provirus integration site and copy number. Expression of K-ras RNA was estimated to be at least 10- to 20-fold higher than that of the mouse cellular homolog of the viral transforming gene. Levels of the virus-coded transforming protein, p21, were similarly elevated, with little variation between nonproducer cells. In two revertant cell lines containing a normal provirus and a rescuable transforming gene, no impairment in expression at either the transcriptional or translational level was found. After superinfection with Kirsten murine sarcoma virus, one revertant became more tumorigenic, whereas the other remained nontumorigenic. These results show that cell transformation by Kirsten murine sarcoma virus is invariably associated with elevated expression of the virus-coded oncogene and that one of the revertants is resistant to the action of the viral transforming gene.