Functional alterations in protein kinase C beta II expression in melanoma

John P. Voris, Leonid A. Sitailo, Heidi R. Rahn, Ann Defnet, Aaron T. Gerds, Robert Sprague, Vipin Yadav, I. Caroline Le Poole, Mitchell F. Denning

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)216-224
Number of pages9
JournalPigment Cell and Melanoma Research
Volume23
Issue number2
DOIs
StatePublished - Apr 2010

Keywords

  • Melanocyte
  • Melanoma
  • Mitochondria
  • PKC
  • Reactive oxygen species
  • UV radiation

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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