Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation.
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.
Department of Dermatology and Social, Osaka University Graduate School of Medicine, Japan.
Shigetoshi
S
Sano
Keith Syson
KS
Chan
Masahiro
M
Kira
Ken
K
Kataoka
Satoshi
S
Takagi
Masahito
M
Tarutani
Satoshi
S
Itami
Kaoru
K
Kiguchi
Masayuki
M
Yokoi
Kaoru
K
Sugasawa
Toshio
T
Mori
Fumio
F
Hanaoka
Junji
J
Takeda
John
J
DiGiovanni
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000528:radiation effects; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008822:Mice, Transgenic; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D050796:STAT3 Transcription Factor; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D017027:Protein Tyrosine Phosphatases