Functional alterations in protein kinase C beta II expression in melanoma

P>Protein kinase C (PKC) is a heterogeneous family of serine/threonine protein kinases that have different biological effects in normal and neoplastic melanocytes (MCs). To explore the mechanism behind their differential response to PKC activation, we analyzed the expression profile of all nine PKC isoforms in normal human MCs, HPV16 E6/E7 immortalized MCs, and a panel of melanoma cell lines. We found reduced PKC beta and increased PKC zeta and PKC iota expression at both the protein and mRNA levels in immortalized MCs and melanoma lines. We focused on PKC beta as it has been functionally linked to melanin production and oxidative stress response. Re-expression of PKC beta in melanoma cells inhibited colony formation in soft agar, indicating that PKC beta loss in melanoma is important for melanoma growth. PKC beta II, but not PKC beta I, was localized to the mitochondria, and inhibition of PKC beta significantly reduced UV-induced reactive oxygen species (ROS) in MCs with high PKC beta expression. Thus alterations in PKC beta expression in melanoma contribute to their neoplastic phenotype, possibly by reducing oxidative stress, and may constitute a selective therapeutic target.