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 |