Resistance of NIH3T3 cells to v-fes transformation induced by a dominant negative H-ras mutant.

NIH3T3 cells carrying a dominant negative H-ras mutant 116Y acquired resistance to transformation by some PTK oncogenes, i.e., v-fes, v-abl, and v-fms, but were sensitive to viral ras and serine threonine kinase oncogenes, v-raf and v-mos. One clone, designated 1-20, infected with v-fes (1-20 fes) exhibited flat morphology and anchorage-dependent cell growth, as did noninfected 1-20 cells. The 1-20 fes cells expressed v-fes oncogene and produced transforming viruses, although these levels were much lower than those in NIH3T3 cells infected with v-fes (NIH3T3 fes). v-fes mRNAs in NIH3T3 fes cells rapidly increased after infection, while accumulation of the v-fes transcripts in 1-20 fes cells was significantly prolonged. Total tyrosine phosphorylation in both NIH3T3 fes and 1-20 fes cells was correlated with the amounts of pp110v-fes. A few proteins were phosphorylated only in NIH3T3 fes but not in 1-20 fes cells. These results suggest that the cellular ras is involved in a signaling pathway from pp110v-fes and this signal stimulates v-fes expression. Inhibition of the ras function may down-regulate this pathway and result in resistance to transformation by v-fes.