Carcinogenesis, Vol. 20, No. 12, 2305-2310,
December 1999
© 1999 Oxford University Press
Carcinogenesis |
Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine
Department of Oncological Pathology, Cancer Center and
1 Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan
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.
Abbreviations: BBN, N-butyl-N-(4-hydroxybutyl)nitrosamine; COX, cyclooxygenase; EGFR, epidermal growth factor receptor; HBSS, Hank's balanced salt solution (Ca2+/Mg2+-free); NIM, nimesulide; NPH, nodulo-papillary hyperplasia; SH, simple hyperplasia; TCC, transitional cell carcinoma.
2 To whom correspondence should be addressed Email: adenda{at}nmu-gw.cc.naramed-u.ac.jp
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