title: Functional alterations in protein kinase C beta II expression in melanoma.
abstract: 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 PKCbeta and increased PKCzeta and PKCiota expression at both the protein and mRNA levels in immortalized MCs and melanoma lines. We focused on PKCbeta as it has been functionally linked to melanin production and oxidative stress response. Re-expression of PKCbeta in melanoma cells inhibited colony formation in soft agar, indicating that PKCbeta loss in melanoma is important for melanoma growth. PKCbetaII, but not PKCbetaI, was localized to the mitochondria, and inhibition of PKCbeta significantly reduced UV-induced reactive oxygen species (ROS) in MCs with high PKCbeta expression. Thus alterations in PKCbeta expression in melanoma contribute to their neoplastic phenotype, possibly by reducing oxidative stress, and may constitute a selective therapeutic target.
authors.affiliation: The Oncology Institute, Loyola University Chicago, Maywood, IL, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Voris
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Sitailo
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Rahn
authors.forename: Ann
authors.initials: A
authors.lastname: Defnet
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Gerds
authors.forename: Robert
authors.initials: R
authors.lastname: Sprague
authors.forename: Vipin
authors.initials: V
authors.lastname: Yadav
authors.forename: I
authors.initials: I
authors.lastname: Caroline Le Poole
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Denning
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000201:enzymology / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010641:Phenotype; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D064546:Protein Kinase C beta; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; D011493:Protein Kinase C; D064546:Protein Kinase C beta