The effects of v-src expression on the differentiation of embryonal carcinoma cells

We have used replication-defective selectable retroviruses to express inducibly or constitutively the v-src gene in the embryonal carcinoma (EC) cell lines F9, PC13 and P19. High v-src expression in F9 and PC13 cells does not induce or disrupt their differentiation. In contrast, P19 cells expressing high levels of v-src have a 'differentiated' morphology and are unable to respond to signals that normally induce differentiation along the neural or muscle pathways. Regulation of v-src transcription from the inducible human metallothionein (MT) promoter has shown that v-src expression above a threshold level induces differentiation of these cells, as defined by loss of the stem cell marker ECMA-7. These results suggest that v-src expression may be compatible with differentiation events occurring early in embryogenesis, represented by F9 and PC13 cell differentiation, but might disrupt the differentiation of cell types present at later developmental stages.