Influence of cigarette smoking on prostaglandin synthesis and cyclooxygenase-2 gene expression in human urinary bladder cancer.
The present study examines the effect of tobacco smoking on the expression of cyclooxygenase (COX)-2 gene, COX enzymatic activity and prostaglandin (PG) synthesis in urothelial mucosal tissues from patients with bladder cancer and from normal individuals. The detection frequency of COX-2 mRNA was 2-fold higher in bladder cancer patients compared to controls and it was accompanied by a significantly increased COX enzymatic activity and PGE2 synthesis (p < 0.05). Smokers, in both control and patients groups, had higher COX-2 expression, COX activity, and PGE2 synthesis compared to the nonsmokers (p < 0.05). The number of cigarettes smoked in the cases, but not controls, correlated well with COX enzymatic activity (r = 0.42, p = 0.016). The observed over-expression of COX-2 gene in human urinary bladder and the concomitant increases in PG synthesis may explain, at least in part, the mechanism by which cigarette smoking influences the development of urothelial neoplasia.
Division of Population Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. af_badawi@fccc.edu
Alaa F
AF
Badawi
Samy L
SL
Habib
Mohammed A
MA
Mohammed
Ahmed A
AA
Abadi
Michael S
MS
Michael
D000368:Aged; D016022:Case-Control Studies; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000503:physiopathology*; D019459:Urothelium / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone