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 differe ntiated phenotype. To determine if these findings had general applicab ility to murine melanomas, we investigated the relationship between se nsitivity to RA and induction of PKC alpha in three different murine m elanoma cell lines. RA inhibited the anchorage-dependent growth of all three cell lines, with JB/MS being the most sensitive, S91 intermedia te, and RPMI the least affected. RA also inhibited soft agar colony fo rmation in JB/MS, but had little effect on RPMI. All cell lines expres sed 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 sm aller 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 thi s density-dependent increase in PKC alpha occurred in three out of fou r melanoma cell lines examined. These results suggest that PKC alpha p lays an important role in RA-induced murine melanoma cell differentiat ion. (C) 1996 Academic Press, Inc.