A series of retroviral vectors have been ' constructed that incorporate dominant selectable markers in conjunction with oncogenes expressed from an inducible promoter. Previous work had shown that expression of an oncogene (v-rasH) under control of the steroid-regulated MMTV promoter could render NIH 3T3 cells conditionally transformed; i.e., cells were only transformed when the promoter was induced by steroid. These vectors have now been utilized to introduce the ras,gene into normal epithelial liver cells. Infection with the retroviral vectors expressing the ras oncogene results in transformation of the liver cells, as monitored by a variety of parameters. Furthermore, some markers of the neoplastic state (growth kinetics and increased glucose uptake) were modulated by increasing the rate of ras gene expression by induction with glucocorticoids. Gross morphological parameters of transformation were not responsive to hormone treatment, although this quality of phenotype switching was also not seen in most of the cell lines generated earlier with the NIH 3T3 cells and may simply reflect the smaller population of transformants that was characterized in the liver cell experiments. These experiments further demonstrate the utility of vectors modelled on this series for the efficient convection of sequences into target cells of-interest and subsequent regulated expression of the introduced oncogene.
