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Functional alterations in protein kinase C beta II expression in melanoma
Author(s) -
Voris John P.,
Sitailo Leonid A.,
Rahn Heidi R.,
Defnet Ann,
Gerds Aaron T.,
Sprague Robert,
Yadav Vipin,
Caroline Le Poole I.,
Denning Mitchell F.
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00664.x
Subject(s) - melanoma , cancer research , beta (programming language) , protein kinase a , biology , microbiology and biotechnology , expression (computer science) , computational biology , kinase , genetics , computer science , programming language
Summary 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 PKCβ and increased PKCζ and PKCι expression at both the protein and mRNA levels in immortalized MCs and melanoma lines. We focused on PKCβ as it has been functionally linked to melanin production and oxidative stress response. Re‐expression of PKCβ in melanoma cells inhibited colony formation in soft agar, indicating that PKCβ loss in melanoma is important for melanoma growth. PKCβII, but not PKCβI, was localized to the mitochondria, and inhibition of PKCβ significantly reduced UV‐induced reactive oxygen species (ROS) in MCs with high PKCβ expression. Thus alterations in PKCβ expression in melanoma contribute to their neoplastic phenotype, possibly by reducing oxidative stress, and may constitute a selective therapeutic target.