Reversal of divergent differentiation by ras oncogene-mediated transformation

In embryogenesis, ovarian surface epithelial cells and ovarian granulosa cells arise through divergent differentiation from a common mesenchymal precursor, the urogenital ridge. In the adult rat, ovarian surface epithelial cells are nonsteroidogenic and keratin positive, while ovarian granulosa cells are steroidogenic and keratin negative. In culture, Kirsten murine sarcoma virus-transformed, tumorigenic ovarian surface epithelial cells continued to express keratin but also became steroidogenic. Transformed ovarian granulosa cells remained steroidogenic but also acquired keratins. Mesodermally derived cells from other sources did not show these differentiation-related changes in response to transformation. The results suggest that v-ras oncogenes may cause the reversion of adult, developmentally related cells to the phenotype of a common, multipotential precursor. They also demonstrate the capacity of v-ras to either induce or reduce the same differentiated characteristic, depending on the developmental history of the target cells.