Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1.
Current evidence suggests that melanogenesis is controlled by epidermal paracrine modulators. We have analyzed the effects of transforming growth factor-beta1 (TGF-beta1) on the basal melanogenic activities of B16/F10 mouse melanoma cells. TGF-beta1 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-beta1 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-beta1 on the melanogenic activity of B16/F10 cells.
Martínez-Esparza
M
M
Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, 30100 Espinardo, Murcia, Spain.
Jiménez-Cervantes
C
C
Beermann
F
F
Aparicio
P
P
Lozano
J A
JA
García-Borrón
J C
JC
D000818:Animals; D006207:Half-Life; D006868:Hydrolysis; D007700:Kinetics; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase