SUPPRESSION OF V-SRC TRANSFORMATION IN PRIMARY RAT EMBRYO FIBROBLASTS

To understand the mechanism for resistance of primary cultures of rat embryo fibroblasts (REFs) to oncogene-induced transformation, we studi ed the transforming ability of a recombinant retrovirus, ZSV, containi ng v-src and neo genes in REFs and in the rat cell line F2408. The sus ceptibility of REFs to p60(v-src) transformation was markedly reduced when compared with that of F2408 cells, despite high levels of express ion of functional p60(v-src) tyrosine kinase in the two systems, In hy brid cells obtained by somatic cell fusion between F2408 cells transfo rmed by v-src and uninfected REFs, the transformed phenotype was suppr essed despite persistent expression of p60(v-src) tyrosine kinase, On the other hand, hybrid cells between v-src transformed F2408 cells and uninfected F2408 cells retained the transformed phenotypes, These res ults indicate that primary cells possess an intracellular function(s) that cause suppression of the transformed phenotype induced by the v-s rc gene, In ZSV-infected REFs, tyrosine phosphorylation of cellular pr oteins, including p125 focal adhesion kinase, p70 paxillin and p130 wa s similar to that in the ZSV-infected F2408 cells, indicating that tyr osine phosphorylation of these proteins is not sufficient for the expr ession of transformed phenotype, On the other hand, cellular fibronect in and one of integrin receptors were downregulated in the ZSV-transfo rmed F2408 cells but not in ZSV-infected REFs, suggesting that fibrone ctin and/or its receptor might play a role in suppressing v-src transf ormation in primary rat cells.