Alterations in gene expression and signal transductions in human melanocytes and melanoma cells.

The development of techniques to cultivate human primary melanocytes in vitro has provided the technical foundation for understanding the biology of this cell. Human melanocytes require various growth factors and agents for proliferation in vitro. These compounds activate two major signal transduction pathways: a calcium- and phospholipid-dependent (protein kinase C or PKC) pathway and a cyclic AMP (cAMP)-dependent (protein kinase A or PKA) pathway. Alterations in these signal transduction pathways coupled with changes in specific genes (protooncogenes, growth factors, and tumor suppressor genes) have been observed in human melanoma cells compared with normal melanocytes. Our own work indicates that loss in the expression of the PKC beta II isotype is a common, if not universal, alteration that occurs early in human melanocyte transformation. In this review, we concentrate on alterations in the signal transduction pathways in human melanocytes and melanoma cells and delineate how an understanding of these changes may allow us to understand the molecular mechanisms involved in human melanocyte transformation.