MSH inhibits growth in a line of amelanotic hamster melanoma cells and induces increases in cyclic AMP levels and tyrosinase activity without inducing melanogenesis.
In Bomirski Ab amelanotic hamster melanoma cells, L-tyrosine and/or L-dopa induce increases in tyrosinase activity as well as synthesis of melanosomes and melanin. L-tyrosine also modifies melanocyte-stimulating hormone (MSH) binding. In this paper we show that in the Bomirski amelanotic melanoma system MSH and agents that raise intracellular cyclic AMP induce dendrite formation, inhibit cell growth, and cause substantial increases in tyrosinase activity without inducing melanin synthesis. Tyrosinase activity is detected only in broken cell preparations, or cytochemically in fixed cells. In the continued absence of mature melanosomes, the induced enzyme remains in elements of the trans-Golgi reticulum. Comparative measurements of cyclic AMP in amelanotic and tyrosine-induced melanotic cells show similar basal levels. L-tyrosine and L-dopa have little or no effect, whereas MSH may cause a 1000% peak increase in cyclic AMP levels both in amelanotic and melanotic cells. None of these agents influences cyclic GMP or inositol trisphosphate (InsP3) levels. In agreement with the InsP3 assays, phorbol ester (TPA) has no effect on melanization, tyrosinase activity or cell proliferation. In conclusion, in the Bomirski amelanotic melanoma, MSH induces only partial cell differentiation associated with raised levels of cyclic AMP. Induction of melanosome synthesis and melanization by L-tyrosine or L-dopa appear to follow pathways unrelated to cyclic AMP, cyclic GMP or InsP3.
Slominski
A
A
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06510.
Moellmann
G
G
Kuklinska
E
E
D000818:Animals; D004156:Catechol Oxidase / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000494:pharmacology
D008543:Melanins; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate