Journal Article

Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by <i>N</i>-butyl-<i>N</i>-(4-hydroxybutyl) nitrosamine

Wakashi Kitayama, Ayumi Denda, Eijiro Okajima, Toshifumi Tsujiuchi and Yoichi Konishi

in Carcinogenesis

Volume 20, issue 12, pages 2305-2310
Published in print December 1999 | ISSN: 0143-3334
Published online December 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.12.2305
Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine

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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.

Keywords: 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.

Journal Article.  4017 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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