Mitogen-Activated Protein Kinase Activation in UV-Induced Signal Transduction

Abstract

Experimental evidence supported by epidemiological findings suggests that solar ultraviolet (UV) irradiation is the most important environmental carcinogen leading to the development of skin cancers. Because the ozone layer blocks UVC (wavelength, 180 to 280 nm) exposure, UVA (UVA I, 340 to 400 nm; UVA II, 320 to 340 nm) and UVB (280 to 320 nm) are probably the chief carcinogenic components of sunlight with relevance for human skin cancer. Substantial contributions to the elucidation of the specific signal transduction pathways involved in UV-induced skin carcinogenesis have been made over the past few years, and most evidence suggests that the cellular signaling response is UV wavelength-dependent. The mitogen-activated protein kinase (MAPK) signaling cascades are targets for UV and are important in the regulation of the multitude of UV-induced cellular responses. Experimental studies have used a range of UVA, UVB, UVC, and various combinations in multiple doses, and the observed effects on activation and phosphorylation of MAPKs are varied. This review focuses on the mechanistic data supporting a role for MAPKs in UV-induced skin carcinogenesis. Progress in understanding the mechanisms of UV-induced signal transduction could lead to the use of these protein kinases as specific targets for the prevention and control of skin cancer.

Protection of normal human reconstructed epidermis from UV by catalase overexpression

“…These findings are consistent with the existence of distinct responses to UVA and UVB irradiation in keratinocytes. [57][58][59] In summary, this study establishes that CAT gene transfer can prevent a sizable part of the deleterious effects of both UVA and UVB irradiation on normal skin by reduction of UV-induced DNA damage as well as regulation of gene expression or cascade activation via cellular redox modulation. To confirm the effectiveness of CAT overexpression in reduction of UV-induced apoptosis as well as the risk of photocarcinogenesis, the study of xenografted reconstructs on tolerant mice 60 exposed to chronic irradiation as well as clinical trials using topical delivery systems at the protein level are necessary.…”

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

“…Initially characterized by activation of the immediate early genes, c-fos and c-jun and various transcription factors including NFκB (Heck et al, 2004), more recent studies have demonstrated that PI3K/Akt and MAP kinase signaling are also key to the response (Bode and Dong, 2003). We found that MAP kinase and Akt were readily activated by UVB in mouse keratinocytes; however, this response was differentiation-dependent.…”

Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-κB signaling

“…Members of the MAPK family are important upstream regulators of transcription factor activities and their signaling is critical to the transduction of a wide variety of extracellular stimuli into intracellular events. The phosphorylation of MAPK molecules controls the activities of various downstream transcription factors implicated in proliferation, differentiation and tumor promotion [46]. ERK1/2 has been shown to be strongly activated by tumor promoters and UV radiation, and has an important role in transmitting signals initiated by them [47].…”