Genetic Deletion of TNFα Inhibits Ultraviolet Radiation-Induced Development of Cutaneous Squamous Cell Carcinomas in PKCε Transgenic Mice via Inhibition of Cell Survival Signals

The study demonstrated that the genetic deletion of TNFα in PKCε transgenic mice inhibited the development of cutaneous squamous cell carcinomas (SCC) induced by ultraviolet radiation (UVR) or the DMBA-TPA protocol. The absence of TNFα in these mice led to increased latency and decreased incidence of SCC. This inhibition was associated with reduced expression of TNFα receptors, cell proliferation markers, and metastatic markers, as well as decreased activation of transcription factors Stat3 and NF-kB, and reduced proliferation of hair follicle stem cells and epidermal hyperplasia. The findings provided genetic evidence linking TNFα to PKCε-mediated sensitivity to SCC development.