COORDINATED MESSENGER-RNA EXPRESSION OF C-KIT WITH TYROSINASE AND TRP-1 IN MELANIN PIGMENTATION OF NORMAL AND MALIGNANT HUMAN MELANOCYTES AND TRANSIENT ACTIVATION OF TYROSINASE BY KIT/SCF-R

The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity, Activation of c-Kit Induces cell proliferation, differentiation or migration among different cell types. The present study provides evidence that c-Kit plays an important role in the cell differentiation rather than in cell proliferation in pigment cells, We found that normal human melanocytes and a limited number of melanoma cells, e.g, WM35, WM39 and G361 cell lines, expressed the c-Kit gene together with tyrosinase and TRP-1 genes. When exposed to alpha-melanocyte stimulating hormone, these three cell lines also showed an increased tyrosinase (dopa-oxidase) activity. By incubating these cells with 20 ng/ml of stem cell factor (SCF) which is a ligand of c-Kit receptor, we found a transient increase of tyrosinase activity 2-4 h post-incubation, indicating an early response of tyrosinase activation, either by elevating tyrosinase protein expression or by tyrosinase protein modification (e.g, phosphorylation). However, Western blot analysis using anti-tyrosinase antibody suggested that there was no change of tyrosinase protein expression between SCF-treated and non-treated cells, We therefore suggest that protein modulation of tyrosinase (e,g. phosphorylation) plays an important role in c-Kit-induced melanogenesis.