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-
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
,
Celia
Jiménez-Cervantes
,
Friedrich
Beermann
¶
,
Pedro
Aparicio
,
José Antonio
Lozano
and
José Carlos
García-Borrón
From the
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-
1 (TGF-
1) on the basal
melanogenic activities of B16/F10 mouse melanoma cells. TGF-
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-
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-
1 on the melanogenic activity of B16/F10 cells.