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 tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun-protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at approximately 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.
Buckman
S Y
SY
Washington University School of Medicine, St Louis, MO, USA.
Gresham
A
A
Hale
P
P
Hruza
G
G
Anast
J
J
Masferrer
J
J
Pentland
A P
AP
D002280:Basal Cell Carcinoma / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D015603:Keratinocytes / Q000201:enzymology / Q000528:radiation effects; D007642:Keratosis / Q000201:enzymology; D008565:Membrane Proteins; D009381:Neoplasms, Radiation-Induced / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012867:Skin / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000209:etiology; D014466:Ultraviolet Rays
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases