Signal transducer and activator of transcription 3 (Stat3) is one of a family of 
cytoplasmic proteins that participate in normal cellular responses to cytokines 
and growth factors as transcription factors. Stat3 modulates various 
physiological functions including cell survival, cell-cycle regulation, and 
angiogenesis through regulation of gene expression, and its constitutive 
activation is associated with a number of human epithelial cancers. Recent 
studies with skin-specific gain and loss of Stat3 function transgenic mice have 
shown that Stat3 plays critical roles in skin carcinogenesis. Multistage skin 
carcinogenesis bioassays performed with these transgenic mice clearly 
demonstrate that Stat3 is required for both tumor initiation and promotion 
through regulation of genes involved in survival and proliferation, 
respectively. Stat3 also plays a role in malignant progression of skin tumors by 
regulating genes that are involved in angiogenesis and invasion. Further studies 
have revealed that Stat3 plays a critical role in epidermal cell proliferation 
and survival following exposure to ultraviolet B (UVB) irradiation. In addition, 
Stat3 is constitutively active in UVB-induced skin tumors from both mice and 
humans. Collectively, these studies suggest that Stat3 may be a potential target 
for both the prevention and treatment of human epithelial cancers including skin 
cancer.