Ultraviolet B exposure activates Stat3 signaling via phosphorylation at tyrosine705 in skin of SKH1 hairless mouse: a target for the management of skin cancer?
Understanding the molecular determinants of ultraviolet (UV) response may lead to the development of novel targets; and therefore, better approaches for the management of cancers, which mainly arise due to the exposure of skin to UV (particularly its UVB spectrum). Signal transducer and activator of transcription (Stat) proteins have been shown to activate multiple signaling pathways to contribute to oncogenesis. Here, we studied the regulation of Stat3 during UVB exposure-mediated responses in the skin of SKH-1 hairless mouse, a model regarded to possess relevance to human situations. Our data demonstrated that a single UVB (180 mJ/cm(2)) exposure to the skin of SKH-1 hairless mice resulted in significant upregulation in (i) protein levels of Stat3 and (ii) phosphorylation of Stat3 at tyrosine(705). Further, the activation of Stat3 was found to be associated with a decrease in apoptotic response of UVB and a gradual time-dependent increase in leukocyte infiltration and hyperplasia. In conclusion, we have demonstrated, for the first time, that UVB exposure to skin resulted in an activation of pro-survival protein Stat3. Based on our observation, we suggest that Stat3 could serve as a target for the management of UVB exposure-mediated damages including skin cancer.
Ahsan
Haseeb
H
Department of Dermatology, University of Wisconsin, Madison, USA.
Aziz
Moammir Hasan
MH
Ahmad
Nihal
N
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D010766:Phosphorylation / Q000528:radiation effects; D011829:Radiation Dosage; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000378:metabolism / Q000628:therapy; D015534:Trans-Activators / Q000378:metabolism* / Q000528:radiation effects; D014443:Tyrosine / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014443:Tyrosine