Analysis of function of protein kinase C isozymes in pigment cells by gene transfection using adenovirus vectors

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We constructed recombinant adenovirus vectors for protein kinase C (PKC) isozymes (α, β, δ, ε, ζ), interleukin-8 (IL-8), constitutively active and dominant negative mutants of phosphatidylinositol 3-kinase (PI 3-kinase), and constitutively active mutant of Akt. Using these adenovirus vectors, we got several results as follows.1. PKCα augments TPA-induced activation of phospholipase D in G361 melanoma cells which do not express PKCα.2. IL-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts.3. PI 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells.4. Elimination of CD4+T cells enhances antitumor effect of locally secreted interleukin-12 on B16 mouse melanoma and induces vitiligo-likecoat color alteration.