Roles Of Cyclooxygenase-1 and -2 In UV-induced Skin Canc

Environmental Health Sciences

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Abstract

Epidemiology studies indicate that ultraviolet (UV) radiation causes skin damage and is a major environmental agent in the causation of skin cancer. The effects of COX-1 and COX-2 deficiency, as well as COX-1 and COX-2 selective inhibitors, in acute UV dose induced skin damage have been studied. The results indicate that COX-2-/-, but not COX-1-/-, mice exhibit increased epidermal damage and a 2.5-fold increased apoptosis compared to wild type mice following UVB exposure. The prostaglandin E2 (PGE2) receptors, EP2 and EP4, have been demonstrated to be involved in COX-2's protective effect against UV induced skin damage and apoptosis. The signaling pathways activated by EP2 and EP4 in the protection against UVB induced skin damage and apoptosis have been partially elucidated, and shown to involve PKA and Akt activation, respectively, and the phosphorylation of BAD.