title: Induction of protein kinase C in mouse melanoma cells by retinoic acid.
abstract: Retinoic acid inhibits the proliferation of B16 mouse melanoma cells. It also eliminates the ability of these cells to grow in soft agar. These biological actions of retinoic acid have been shown to be accompanied by an increase in the amount of cyclic AMP-dependent protein kinase and an induction of a new isozyme form (RII beta). In this report we demonstrated that retinoic acid-treated B16 melanoma cells had large increases in protein kinase C activity. This increased enzyme activity was accompanied by increases in both the number of phorbol dibutyrate binding sites and the amount of immunoreactive protein kinase C. Other treatments (melanocyte-stimulating hormone, serum deprivation) which inhibited the growth of these cells did not increase protein kinase C activity. When B16 melanoma cells were treated for a prolonged time (72 h) with phorbol dibutyrate, protein kinase C activity was barely detectable. Under these conditions, melanin production was inhibited and cell growth was accelerated. When retinoic acid was added together with phorbol dibutyrate, it prevented the growth stimulatory effect of the phorbol ester and increased protein kinase C activity. However, the absolute activity of the enzyme was still below that found in control cells and very much lower than in cells treated with retinoic acid alone. Taken together with our previous findings, we propose that the increase in protein kinase C might be part of a differentiation program induced by retinoic acid.
authors.affiliation: Department of Biochemistry Boston University School of Medicine, Massachusetts 02118.
authors.forename: R M
authors.initials: RM
authors.lastname: Niles
authors.forename: B P
authors.initials: BP
authors.lastname: Loewy
mesh_terms: D015153:Blotting, Western; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015240:Phorbol 12,13-Dibutyrate; D014212:Tretinoin; D011493:Protein Kinase C