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Volume 272, Number 7, Issue of February 14, 1997 pp. 3967-3972
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Transforming Growth Factor-beta 1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

(Received for publication, August 12, 1996, and in revised form, October 18, 1996)

María Martínez-Esparza Dagger , Celia Jiménez-Cervantes Dagger , Friedrich Beermann , Pedro Aparicio Dagger , José Antonio Lozano Dagger and José Carlos García-Borrón Dagger

From the Dagger  Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, 30100 Espinardo, Murcia, Spain, and the  Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, 1066 Epalinges, Switzerland

Current evidence suggests that melanogenesis is controlled by epidermal paracrine modulators. We have analyzed the effects of transforming growth factor-beta 1 (TGF-beta 1) on the basal melanogenic activities of 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% of the control values but had no effect on dopachrome tautomerase activity (TRP-2). The inhibition affected to similar extents the Dopa oxidase activity associated to tyrosinase-related protein-1 (TRP-1) and tyrosinase. This inhibition was noticeable between 1 and 3 h after the addition of the cytokine, and maximal after 6 h of treatment. The decrease in the enzymatic activity was paralleled by a decrease in the abundance of the TRP-1 and tyrosinase proteins. TGF-beta 1 mediated this effect by increasing the rate of degradation of tyrosinase and TRP-1. Conversely, after 48 h of treatment, the expression of the tyrosinase gene decreased only slightly, while TRP-1 and TRP-2 gene expression was not affected. An increased rate of proteolytic degradation of TRP-1 and tyrosinase seems the main mechanism accounting for the inhibitory effect of TGF-beta 1 on the melanogenic activity of B16/F10 cells.


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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.