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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 WM1115. 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. (C) 2002 Lippincott Williams Wilkins

nPKCdelta is a phospholipid-dependent and calcium-independent PKC isoform, whose over expression in BL6T murine melanoma cells, modifies their proliferative and metastatic potential in vivo, We focus here on the possible relationship between the subcellular localisation of nPKCdelta and distinct phase of the cell cycle. Our findings show a dynamic localisation of nPKCdelta in dependence of the phase of the cell cycle. Actually, this isoform is preferentially localised to the cytoplasm in serum-starved cells, shifting to the nucleus during the S-phase and becoming peri-nuclear, associated to the Golgi apparatus, in G2-M phase. Therefore, taken together our findings demonstrate that the subcellular localisation of nPKCdelta changes dynamically during the cell cycle in dependence of the requirement of the enzyme at a particular place of the cell. (C) 2002 Elsevier Science (USA). All rights reserved.