Induction of tumorigenicity and lack of in vitro growth requirement for 12-O-tetradecanoylphorbol-13-acetate by transfection of murine melanocytes with v-Ha-ras.

A nontumorigenic line of murine melanocytes, Mel-ab, has been transfected with the v-Ha-ras gene under transcriptional control of the Moloney murine leukemia virus long terminal repeat. Transfectants produced rapidly growing undifferentiated melanomas in recipient mice. The inhibition of melanin production in transformed cells, observable both in vitro and in vivo, suggests that ras may affect melanocyte cytodifferentiation. Mel-ab cells require the continual presence of 12-O-tetradecanoylphorbol-13-acetate, or other activators of protein kinase C, for in vitro growth. Transfectants expressing v-Ha-ras no longer manifested this requirement and were actually growth inhibited by the addition of protein kinase C activators. These results are consistent with the notion that ras acts via the protein kinase C pathway in conferring autonomous growth on Mel-ab cells.