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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Ultraviolet radiation and 12-O-tetradecanoylphorbol-13-acetate-induced interaction of mouse epidermal protein kinase Cýý with Stat3 involve integration with ERK1/2.

Authors: Sand, Jordan Marshall; Bin Hafeez, Bilal; Aziz, Moammir Hasan; Siebers, Emily Marie; Dreckschmidt, Nancy Ellen; Verma, Ajit Kumar

Published In Mol Carcinog, (2012 Apr)

Abstract: We have reported that protein kinase C epsilon (PKCýý) expression level in epidermis dictates the susceptibility of mice to the development of squamous cell carcinomas (SCC) elicited either by repeated exposure to ultraviolet radiation (UVR) or by the DMBA-TPA tumor promotion protocol. To find clues about the mechanism by which PKCýý mediates susceptibility to UVR-induced development of SCC, we found that PKCýý-over-expressing transgenic mice, as compared to their wild-type littermates, when exposed to UVR, elicit enhanced phosphorylation of Stat3 at Ser727 residues. Stat3 is constitutively activated in SCC and UVR fails to induce SCC in Stat3 mutant mice. Stat3Ser727 phosphorylation is essential for Stat3 transcriptional activity (Cancer Res. 67: 1385, 2007). We now present several novel findings including that PKCýý integrates with its downstream partner ERK1/2 to phosphorylate Stat3Ser727. In these experiments, mice were either exposed to UVR (2ýýýkJ/m(2)/dose) emitted by Kodacel-filtered FS-40 sun lamps or treated with TPA (5ýýýnmol). Both UVR and TPA treatment stimulated PKCýý-Stat3 interaction, Stat3Ser727 phosphorylation and Stat3-regulated gene COX-2 expression. PKCýý-Stat3 interaction and Stat3Ser727 phosphorylation was also observed in SCC elicited by repeated UVR exposures of mice. PKCýý-Stat3 interaction was PKCýý specific. UVR or TPA-stimulated Stat3Ser727 phosphorylation accompanied interaction of PKCýý with ERK1/2 in intact mouse skin in vivo. Deletion of PKCýý in wild-type mice attenuated both TPA and UVR-induced expression of phosphoforms of ERK1/2 and Stat3Ser727. These results indicate that PKCýý integrates with ERK1/2 to mediate both TPA and UVR-induced epidermal Stat3Ser727 phosphorylation. PKCýý and Stat3 may be potential molecular targets for SCC prevention.

PubMed ID: 21480396 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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