TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS BASAL MELANOGENESIS IN B16F10 MOUSE MELANOMA-CELLS BY INCREASING THE RATE OF DEGRADATION OF TYROSINASE AND TYROSINASE-RELATED PROTEIN-1/

Current evidence suggests that melanogenesis is controlled by epiderma l paracrine modulators. We have analyzed the effects of transforming g rowth factor-beta 1 (TGF-beta 1) on the basal melanogenic activities o f B16/F10 mouse melanoma cells. TGF-beta 1 treatment (48 h) elicited a concentration-dependent decrease in basal tyrosine hydroxylase and 3, 4-dihydroxyphenylalanine (Dopa) oxidase activities, to less than 30% o f the control values but had no effect on dopachrome tautomerase activ ity (TRP-2). The inhibition affected to similar extents the Dopa oxida se activity associated to tyrosinase-related protein-1 (TRP-1) and tyr osinase. This inhibition was noticeable between 1 and 3 h after the ad dition of the cytokine, and maximal after 6 h of treatment. The decrea se in the enzymatic activity was paralleled by a decrease in the abund ance of the TRP-1 and tyrosinase proteins. TGF-beta 1 mediated this ef fect by increasing the rate of degradation of tyrosinase and TRP-1. Co nversely, after 48 h of treatment, the expression of the tyrosinase ge ne decreased only slightly, while TRP-1 and TRP-2 gene expression was not affected. An increased rate of proteolytic degradation of TRP-1 an d tyrosinase seems the main mechanism accounting for the inhibitory ef fect of TGF-beta 1 on the melanogenic activity of B16/F10 cells.