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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have reported that protein kinase C epsilon (PKCε) 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 PKCε mediates susceptibility to UVR-induced development of SCC, we found that PKCε-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 PKCε integrates with its downstream partner ERK1/2 to phosphorylate Stat3Ser727. In these experiments, mice were either exposed to UVR (2kJ/m2/dose) emitted by Kodacel-filtered FS-40 sun lamps or treated with TPA (5nmol). Both UVR and TPA treatment stimulated PKCε-Stat3 interaction, Stat3Ser727 phosphorylation and Stat3-regulated gene COX-2 expression. PKCε-Stat3 interaction and Stat3Ser727 phosphorylation was also observed in SCC elicited by repeated UVR exposures of mice. PKCε-Stat3 interaction was PKCε specific. UVR or TPA-stimulated Stat3Ser727 phosphorylation accompanied interaction of PKCε with ERK1/2 in intact mouse skin in vivo. Deletion of PKCε in wild-type mice attenuated both TPA and UVR-induced expression of phosphoforms of ERK1/2 and Stat3Ser727. These results indicate that PKCε integrates with ERK1/2 to mediate both TPA and UVR-induced epidermal Stat3Ser727 phosphorylation. PKCε and Stat3 may be potential molecular targets for SCC prevention.

Original languageEnglish (US)
Pages (from-to)291-302
Number of pages12
JournalMolecular Carcinogenesis
Volume51
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Protein Kinase C-epsilon
Tetradecanoylphorbol Acetate
Protein Kinase C
Radiation
Squamous Cell Carcinoma
Phosphorylation
9,10-Dimethyl-1,2-benzanthracene
Solar System
Epidermis
Transgenic Mice

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Ultraviolet radiation and 12-O-tetradecanoylphorbol-13-acetate-induced interaction of mouse epidermal protein kinase Cε with Stat3 involve integration with ERK1/2. / Sand, Jordan Marshall; Hafeez, Bilal; Aziz, Moammir Hasan; Siebers, Emily Marie; Dreckschmidt, Nancy Ellen; Verma, Ajit Kumar.

In: Molecular Carcinogenesis, Vol. 51, No. 4, 01.04.2012, p. 291-302.

Research output: Contribution to journalArticle

Sand, Jordan Marshall ; Hafeez, Bilal ; Aziz, Moammir Hasan ; Siebers, Emily Marie ; Dreckschmidt, Nancy Ellen ; Verma, Ajit Kumar. / Ultraviolet radiation and 12-O-tetradecanoylphorbol-13-acetate-induced interaction of mouse epidermal protein kinase Cε with Stat3 involve integration with ERK1/2. In: Molecular Carcinogenesis. 2012 ; Vol. 51, No. 4. pp. 291-302.
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abstract = "We have reported that protein kinase C epsilon (PKCε) 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 PKCε mediates susceptibility to UVR-induced development of SCC, we found that PKCε-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 PKCε integrates with its downstream partner ERK1/2 to phosphorylate Stat3Ser727. In these experiments, mice were either exposed to UVR (2kJ/m2/dose) emitted by Kodacel-filtered FS-40 sun lamps or treated with TPA (5nmol). Both UVR and TPA treatment stimulated PKCε-Stat3 interaction, Stat3Ser727 phosphorylation and Stat3-regulated gene COX-2 expression. PKCε-Stat3 interaction and Stat3Ser727 phosphorylation was also observed in SCC elicited by repeated UVR exposures of mice. PKCε-Stat3 interaction was PKCε specific. UVR or TPA-stimulated Stat3Ser727 phosphorylation accompanied interaction of PKCε with ERK1/2 in intact mouse skin in vivo. Deletion of PKCε in wild-type mice attenuated both TPA and UVR-induced expression of phosphoforms of ERK1/2 and Stat3Ser727. These results indicate that PKCε integrates with ERK1/2 to mediate both TPA and UVR-induced epidermal Stat3Ser727 phosphorylation. PKCε and Stat3 may be potential molecular targets for SCC prevention.",
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AU - Verma, Ajit Kumar

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