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Regulation of melanogenesis in B16 mouse melanoma cells by protein kinase C
Author(s) -
Mahalingam Harish,
Vaughn James,
Novotny James,
Gruber Joachim R.,
Niles Richard M.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199609)168:3<549::aid-jcp7>3.0.co;2-p
Subject(s) - protein kinase a , melanoma , kinase , microbiology and biotechnology , chemistry , biology , biochemistry , cancer research
Melanogenesis is regulated by a variety of environmental and hormonal factors. In this study, we showed that protein kinase C (PKC) plays a major role in regulating melanogenesis in B16 mouse melanoma cells. Chronic treatment of B16 cells with phorbol dibutyrate resulted in a concentration‐dependent loss of density‐dependent induction of tyrosinase activity, which correlated positively with a concentration‐dependent loss of PKC enzyme activity. In contrast, B16 clones overexpressing PKCα had increased tyrosinase activity. Different phorbol derivatives inhibited tyrosinase activity and depleted cellular PKCα in a manner that reflected their reported tumor‐promoting activity. Western blotting analysis showed that phorbol dibutyrate decreased the amount of the brown locus gene product (TRP‐1) by 50% and lowered the amount of the albino locus gene product (tyrosinase) to undetectable levels. None of the phorbol derivatives affected the level of the slaty locus protein (TRP‐2). The decrease in tyrosinase and TRP‐1 protein levels was found to be due to a decrease in the mRNA encoded by these genes. In addition to inhibiting the density‐dependent increase in tyrosinase activity, phorbol dibutyrate inhibited some, but not all, of the 8‐bromocyclic AMP‐induced increase in tyrosinase activity. This was accompanied by a decrease in the amount of tyrosinase protein induced by 8‐bromocyclic AMP. Although 8‐bromocyclic AMP did not change the level of TRP‐1, it did reverse the decrease in the amount of this protein induced by phorbol dibutyrate. The amount of TRP‐2 was not altered by any of these agents. These data suggest that PKC regulates melanogenesis primarily by controlling the constitutive expression of tyrosinase and, to a lesser extent, TRP‐1. © 1996 Wiley‐Liss, Inc.