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


Authors: Kelley, D. J.; Mestre, J. R.; Subbaramaiah, K.; Sacks, P. G.; Schantz, S. P.; Tanabe, T.; Inoue, H.; Ramonetti, J. T.; Dannenberg, A. J.
Article Title: Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells
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.
Keywords: controlled study; human cell; promoter region; pathogenesis; dose response; cells, cultured; gene expression; membrane proteins; carcinogenesis; genetic transfection; messenger rna; cell transformation; cyclooxygenase 2; prostaglandin e2; benzo[a]pyrene; benzo(a)pyrene; mouth mucosa; isoenzymes; enzyme induction; gene expression regulation, enzymologic; polycyclic aromatic hydrocarbon; prostaglandin synthesis; dinoprostone; tobacco smoke; prostaglandin-endoperoxide synthases; humans; human; priority journal; article
Journal Title: Carcinogenesis
Volume: 18
Issue: 4
ISSN: 0143-3334
Publisher: Oxford University Press  
Date Published: 1997-04-01
Start Page: 795
End Page: 799
Language: English
DOI: 10.1093/carcin/18.4.795
PUBMED: 9111217
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Peter G Sacks
    53 Sacks
  2. Stimson P Schantz
    115 Schantz
  3. Juan R Mestre
    10 Mestre