ALTERATIONS IN GENE-EXPRESSION AND SIGNAL TRANSDUCTIONS IN HUMAN MELANOCYTES AND MELANOMA-CELLS

The development of techniques to cultivate human primary melanocytes i n vitro has provided the technical foundation for understanding the bi ology of this cell. Human melanocytes require various growth factors a nd agents for proliferation in vitro. These compounds activate two maj or signal transduction pathways: a calcium and phospholipid-dependent (protein kinase C or PKC) pathway and a cyclic AMP (cAMP)-dependent (p rotein kinase A or PKA) pathway. Alterations in these signal transduct ion pathways coupled with changes in specific genes (protooncogenes, g rowth factors, and tumor suppressor genes) have been observed in human melanoma cells compared with normal melanocytes. Our own work indicat es that loss in the expression of the PKC beta(II) isotype is a common , if not universal, alteration that occurs early in human melanocyte t ransformation. In this review, we concentrate on alterations in the si gnal transduction pathways in human melanocytes and melanoma cells and delineate how an understanding of these changes may allow us to under stand the molecular mechanisms involved in human melanocyte transforma tion.