Resistance to Transformation by Insertionally Activated c-erbB Is a Dominant Phenotype in Fibroblasts

Tissue-specific factors influence whether cells are susceptible to transformation by erbB oncogenes. Avian fibroblasts resist transformation by insertionally activated c-erbB (IAc-erbB), whereas erythroblasts are transformed by this mutant of the epidermal growth factor receptor. In studies presented here, NIH/3T3 cells resisted transformation by IAc-erbB. This finding indicates that the nonpermissiveness of fibroblasts is conserved between avian and murine species. Surprisingly, expression of IAc-erbB blocked transformation by a v-erbB allele. The trans-dominant interference by IAc-erbB occurred despite expression at levels lower than for v-erbB. Together with previous reports, the results indicate that IAc-erbB can exert opposite growth effects in different tissues. The switch from positive to negative growth regulation, which depends on the cellular context, provides novel insight into tissue-specific regulation of receptor tyrosine kinases. Evasion of cell-specific inhibition apparently contributes to the distinct tissue tropisms of various erbB mutants.