Ionizing radiation up-regulates cyclooxygenase-2 in I407 cells through p38 mitogen-activated protein kinase

Teresa G. Tessner, Filipe Muhale, Suzanne Schloemann, Steven Cohn, Aubrey R. Morrison, William F. Stenson

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The epithelial cell line I407 up-regulates cyclooxygenase-2 (COX-2) mRNA and protein expression following ionizing radiation exposure. Prostaglandin E2 (PGE2) production is concomitantly up-regulated. Irradiation of I407 cells also results in phosphorylation of the p38 mitogen-activated protein kinase and the p38 inhibitor SB203580 abrogates radiation-induced PGE2 synthesis. Wild-type p38α (p38αWT) and dominant-negative p38α (p38αDN) stable-transfectant clones of I407 cells were used to examine the role of the p38 mitogen-activated protein kinase pathway in the events controlling PGE2 synthesis after ionizing radiation. Treatment of p38αWT clones with γ-radiation resulted in increased COX-2 protein levels and PGE2 synthesis similar to treated control-transfected cells. In contrast, the p38αDN clones failed to up-regulate COX-2 protein or increase PGE2 synthesis when irradiated. Exogenous arachidonate did not restore PGE2 synthesis by p38αDN cells. Radiation increased COX-2 mRNA stability and the p38 inhibitor SB203580 attenuated COX-2 mRNA stability in irradiated I407 cells. In contrast, irradiation had no effect on transcription from a COX-2 promoter/luciferase reporter plasmid in the presence or absence of SB203580. The data demonstrate a crucial role for p38α in COX-2 expression and PGE2 synthesis in an irradiated transformed epithelial cell line. Furthermore, they indicate that p38 activity is required at a step distal to arachidonate release, most probably COX-2 up-regulation, since exogenous arachidonate did not restore PGE2 synthesis.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalCarcinogenesis
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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