Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells

Daniel J. Kelley, Juan R. Mestre, Kotha Subbaramaiah, Peter G. Sacks, Stimson P. Schantz, Tadashi Tanabe, Hiroyasu Inoue, John T. Ramonetti, Andrew J. Dannenberg

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin biosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (Cox-2) mRNA, protein and synthesis of prostaglandin E2 (PGE2) in normal and transformed oral epithelial cells. Treatment with B[a]P caused a dose-dependent increase in production of PGE2, with a maximal increase of ~100%. Enhanced synthesis of PGE2 was associated with increased amounts of Cox-2 protein. B[a]P also caused a two-fold increase in Cox-2 mRNA in both normal and transformed cells. Transient transfections with a Cox-2 promoter construct showed that B[a]P-mediated induction of Cox-2 mRNA reflected increased transcription. Levels of Cox-1 were unaffected by B[a]P. B[e]P did not affect the synthesis of PGE2 or amounts of Cox-2. These data are important because B[a]P-mediated induction of Cox-2 may predispose to carcinogenesis by enhancing the production of mutagens and the synthesis of prostaglandins.

Original languageEnglish (US)
Pages (from-to)795-799
Number of pages5
JournalCarcinogenesis
Volume18
Issue number4
DOIs
StatePublished - Apr 1997

ASJC Scopus subject areas

  • Cancer Research

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