The relationship between susceptibility to retinoic acid treatment and protein kinase C alpha expression in murine melanoma cell lines.

Retinoic acid (RA)-induced differentiation of B16 mouse melanoma cells is accompanied by a large increase in the amount of PKCalpha protein. Overexpression of PKCalpha in these cells results in a more differentiated phenotype. To determine if these findings had general applicability to murine melanomas, we investigated the relationship between sensitivity to RA and induction of PKCalpha in three different murine melanoma cell lines. RA inhibited the anchorage-dependent growth of all three cell lines, with JB/MS being the most sensitive, S91 intermediate, and RPMI the least affected. RA also inhibited soft agar colony formation in JB/MS, but had little effect on RPMI. All cell lines expressed PKCalpha, but not beta or gamma. RA induced a large concentration-dependent increase in PKCalpha protein in JB/MS (6- to 10-fold), a smaller increase in S91 (2- to 3-fold), and very little induction of PKCalpha in RPMI. Previously we had observed that the amount of PKCalpha increased with the density of B16 cells in culture. We found that this density-dependent increase in PKCalpha occurred in three out of four melanoma cell lines examined. These results suggest that PKCalpha plays an important role in RA-induced murine melanoma cell differentiation.