| Autor: |
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. |
| Zdroj: |
Pigment Cell Research; April 2010, Vol. 23 Issue: 2 p216-224, 9p |
| Abstrakt: |
Protein kinase C (PKC) is a heterogeneous family of serinethreonine 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 E6E7 immortalized MCs, and a panel of melanoma cell lines. We found reduced PKC and increased PKC and PKC expression at both the protein and mRNA levels in immortalized MCs and melanoma lines. We focused on PKC as it has been functionally linked to melanin production and oxidative stress response. Re-expression of PKC in melanoma cells inhibited colony formation in soft agar, indicating that PKC loss in melanoma is important for melanoma growth. PKCII, but not PKCI, was localized to the mitochondria, and inhibition of PKC significantly reduced UV-induced reactive oxygen species (ROS) in MCs with high PKC expression. Thus alterations in PKC expression in melanoma contribute to their neoplastic phenotype, possibly by reducing oxidative stress, and may constitute a selective therapeutic target. |
| Databáze: |
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