Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.
The anti-inflammatory drugs, aspirin and piroxicam, are known to possess chemopreventive potential against rat superficial urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Recently, we found similar inhibitory effects with a selective cyclooxygenase (COX)-2 inhibitor, nimesulide. In order to clarify the inhibitory mechanisms, we have further studied the expression of COX-2 protein in urinary bladder tumors induced by BBN in Fischer 344 male rats. For comparison, papillomatosis caused by uracil-induced urolithiasis, and normal epithelial cells, were also investigated. Western blot analysis revealed COX-2 protein to be barely expressed in the normal epithelial cells, whereas it was increased 13-22-fold in varying sizes of urinary bladder tumors and 7-fold in papillomatosis. Immunohistochemically, COX-2 protein was diffusely expressed in transitional cell carcinomas and nodulo-papillary hyperplasia but weakly expressed only in basal cells in simple hyperplasia and normal-looking surrounding epithelia. In papillomatosis, it was moderately expressed only in endothelial cells in stroma. These results indicate that COX-2 plays important roles in the development of preneoplastic and neoplastic lesions in the rat urinary bladder, and therefore could be a good target for chemoprevention of superficial lesions.
Kitayama
W
W
Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Denda
A
A
Okajima
E
E
Tsujiuchi
T
T
Konishi
Y
Y
D000818:Animals; D015153:Blotting, Western; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000201:enzymology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D010212:Papilloma / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000201:enzymology*
D002273:Carcinogens; D007527:Isoenzymes; D008565:Membrane Proteins; D002085:Butylhydroxybutylnitrosamine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat