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 PKC alpha protein. Overexpression of PKC alpha 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 PKC alpha 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 PKC alpha, but not beta or gamma. RA induced a large concentration-dependent increase in PKC alpha protein in JB/MS (6-to 10-fold), a smaller increase in S91 (2-to 3-fold), and very little induction of PKC alpha in RPMI. Previously we had observed that the amount of PKC alpha increased with the density of B16 cells in culture. We found that this density-dependent increase in PKC alpha occurred in three out of four melanoma cell lines examined. These results suggest that PKC alpha plays an important role in RA-induced murine melanoma cell differentiation. (C) 1996 Academic Press, Inc.