Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation

Shigetoshi Sano, Keith Syson Chan, Masahiro Kira, Ken Kataoka, Satoshi Takagi, Masahito Tarutani, Satoshi Itami, Kaoru Kiguchi, Masayuki Yokoi, Kaoru Sugasawa, Toshio Mori, Fumio Hanaoka, Junji Takeda, John DiGiovanni

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

UVB irradiation of signal transducer and activator of transcription 3 (Stat3)-deficient keratinocytes resulted in a high incidence of apoptosis compared with controls. Conversely, forced expression of Stat3 desensitized keratinocytes to UVB-induced apoptosis. Upon UVB exposure, keratinocyte Stat3 was rapidly dephosphorylated, followed by decreases of both Stat3 mRNA and protein levels in a p53-independent manner. Vanadate treatment reversed the UVB-induced down-regulation of Stat3 and generation of apoptotic keratinocytes, suggesting the involvement of a tyrosine phosphatase. Furthermore, Stat3 was required for UVB-induced proliferation of follicular keratinocytes, leading to epidermal thickening. Finally, constitutive activation of Stat3 was observed in UVB-induced squamous cell carcinomas of either mice or human origin. These data suggest that Stat3 is required for survival and proliferation of keratinocytes following UVB exposure and that Stat3 is tightly regulated as part of a novel protective mechanism against UVB-induced skin cancer.

Original languageEnglish (US)
Pages (from-to)5720-5729
Number of pages10
JournalCancer research
Volume65
Issue number13
DOIs
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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