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

Science's STKE  28 Jan 2003:
Vol. 2003, Issue 167, pp. re2
DOI: 10.1126/stke.2003.167.re2

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Sunlight is most likely the main cause of skin cancer, which is the most common human cancer. Solar radiation is categorized by wavelength into ultraviolet C (UVC, wavelength 180 to 280 nm), ultraviolet B (UVB, 280 to 320 nm), and ultraviolet A (UVA) regions (UVA I, 340 to 400 nm; UVA II, 320 to 340 nm). All UV spectra have been linked to cancer in experimental animal models. However, the physiologic relevance of UVC may be dubious because all of the UVC radiation is absorbed by the ozone layer of Earth's atmosphere. UV radiation at Earth's surface consists of 1 to 10% UVB and 90 to 99% UVA and can penetrate human skin, making it the primary target for UV-induced damage and cancer. UV exposure can result in direct or indirect DNA damage, depending on the wavelength and exposure time. Even though DNA damage is a primary initiator in UV-induced skin carcinogenesis, the mechanism behind the tumor-promoting ability of UV is unclear. The assumption in the past was that the mechanisms of UV-stimulated tumor promotion could be based on studies of UVC-induced signal transduction, because the effects were assumed to be similar for all wavelengths of UV. However, accumulating evidence suggests that the cellular responses produced by UV irradiation are likely to be wavelength-dependent. UV activates various signaling pathways that are either oncogenic or protective or both. Many of these pathways are mediated primarily through signaling cascades involving mitogen-activated protein kinases (MAPKs), resulting in the modification of transcription factors such as activator protein-1, which can lead to skin cancer. In light of rising public concern over the increased incidence of skin cancer, this review focuses on the mechanistic data supporting a role for MAPKs in UV-stimulated 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.