COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer

Extensive documentation has validated the role of UV irradiation as a tumorinitiator and promoter, inducing both squamous and basal cell carcinomas.Human epidermis is a tissue which undergoes active metabolism ofarachidonic acid to prostaglandins which is regulated by the action ofprostaglandin H synthase (also known as cyclooxygenase). One mechanism forthe promotional activity of UV light may involve its ability to induceprostaglandin formation. Work in our laboratory has demonstrated that acuteexposure of human keratinocytes to UVB irradiation results in increasedproduction of prostaglandin E2 (PGE2). When cultured human keratinocyteswere examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blotanalysis showed a 6-fold increase in COX-2 protein which was evident at 6 hand peaked 24 h after irradiation. Furthermore, when human subjects wereirradiated on sun- protected skin with up to four times their minimalerythema dosage (MED) and biopsied 24 h later, upregulation of COX-2protein expression was observed via immunofluorescence microscopy. RNAaseprotection assays supported this observation, showing induction of COX-2message which peaked at approximately 12 h following irradiation in vitro.Furthermore, human squamous cell carcinoma biopsies exhibited stronglyenhanced staining for COX-2 protein via immunohistochemistry and Westernanalysis when compared to normal non-sun-exposed control skin. Together,these data demonstrate acute upregulation of COX-2 via UVB irradiation andsuggest the need for further studies of COX-2 expression as a potentialpharmacological target mediating human skin tumor development.