title: Higher levels of melanin and inhibition of cdk2 activity in primary human melanoma cells WM115 overexpressing nPKCdelta.
abstract: Many studies have attempted to define the state of differentiation of melanoma cells and to correlate it with other critical parameters of malignancy such as the tumorigenic and metastatic nature of the cells. In the present paper we focused on the possible relationships between the novel protein kinase C isoform nPKCdelta, melanin synthesis and proliferative capacity in a primary human melanoma cell line WM115. Cells were transfected to produce overexpression of this isoform and the effects on melanin synthesis, cyclin-E dependent kinase (cdk2) activity and cyclin E expression were studied. It was shown that translocation of nPKCdelta into the nucleus affects melanin synthesis and inhibits cdk2 activity. As a compensatory effect, the level of cyclin E increases. In view of these results we suggest a model for the role of nPKCdelta in melanoma cells that may offer a new therapeutic perspective.
authors.affiliation: Department of General Physiology and Biochemistry, Section of General Pathology, University of Milan, Celoria 26, 20133 Milan, Italy. Caterina.LaPorta@unimi.it
authors.forename: Caterina A M
authors.initials: CA
authors.lastname: La Porta
authors.forename: D
authors.initials: D
authors.lastname: Porro
authors.forename: R
authors.initials: R
authors.lastname: Comolli
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002455:Cell Division; D048429:Cell Size; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D051745:Protein Kinase C-delta; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D019927:Cyclin E; D007527:Isoenzymes; D008543:Melanins; D009363:Neoplasm Proteins; D014442:Monophenol Monooxygenase; C497259:Prkcd protein, mouse; D017346:Protein Serine-Threonine Kinases; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases