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Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis

Oncogene volume 28, pages 950–960 (2009)Cite this article

Abstract

In this study, the potential role of Stat3 in UVB-induced skin carcinogenesis was examined using skin-specific gain and loss of function transgenic mice, that is, K5.Stat3C and K5Cre.Stat3fl/fl mice, respectively. The epidermis of Stat3-deficient mice was highly sensitive to UVB-induced apoptosis, whereas the epidermis of K5.Stat3C mice was more resistant to UVB-induced apoptosis. In particular, the status of Stat3 influenced the survival of ultraviolet-photoproduct cells, including those located in the hair follicles. K5.Stat3C mice exhibited significantly increased epidermal proliferation and hyperplasia in response to UVB irradiation, whereas Stat3-deficient mice showed reduced epidermal proliferation and hyperplasia. Expression of target genes regulated by Stat3, such as cyclin D1 and Bcl-xL, was increased in epidermis of both control and UVB-irradiated K5.Stat3C mice, and downregulated in epidermis of both control and UVB-irradiated K5Cre.Stat3fl/fl mice. Following UVB irradiation, the formation of skin tumors in K5.Stat3C mice was accelerated and both the incidence and multiplicity of skin tumors were significantly greater than wild-type controls. In contrast, Stat3-deficient mice were resistant to UVB skin carcinogenesis. These results show that Stat3 plays an important role in the development of UVB-induced skin tumors through its effects on both survival and proliferation of keratinocytes during carcinogenesis.

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Acknowledgements

This study was supported by NCI Grants CA76520, CA105345, University of Texas MD Anderson Cancer Center support Grant CA16672 and National Institute of Environmental Health Sciences Center Grant ES07784. Funding as an Odyssey fellow (to DJ Kim) was supported by the Odyssey Program and the H-E-B award for scientific achievement at the University of Texas MD Anderson Cancer Center.

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Authors and Affiliations

  1. Department of Carcinogenesis, Science Park-Research Division, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA

    D J Kim, J M Angel & J DiGiovanni

  2. Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan

    S Sano

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  1. D J Kim
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  3. S Sano
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Correspondence to J DiGiovanni.

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Kim, D., Angel, J., Sano, S. et al. Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB-induced skin carcinogenesis. Oncogene 28, 950–960 (2009). https://doi.org/10.1038/onc.2008.453

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