Carcinogenesis, Vol 19, 723-729, Copyright © 1998 by Oxford University Press
SY Buckman, A Gresham, P Hale, G Hruza, J Anast, J Masferrer and AP Pentland
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.
ARTICLES
COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer
Washington University School of Medicine, St Louis, MO, USA.
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