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Comparison of Uroplakin Expression During Urothelial Carcinogenesis Induced by N-Butyl-N-(4-Hydroxybutyl)Nitrosamine in Rats and Mice

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA, First Department of Pathology, Nagoya City University Medical School, Nagoya 454, Japan

Margaret St. John

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA

Maria Luiza De Oliveira

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA

Lora Arnold

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA

Tomoyuki Shirai

First Department of Pathology, Nagoya City University Medical School, Nagoya 454, Japan

Tung-Tien Sun

Epithelial Biology Unit, The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, 10016, USA, Department of Pharmacology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA

Samuel M. Cohen

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA, scohen{at}unmc.edu.

The expression of uroplakins, the tissue-specific and differentiation-dependent membrane proteins of the urothelium, was analyzed immunohistochemically in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats and mice during bladder carcinogenesis. Male Fischer 344 rats were treated with 0.05% BBN in the drinking water for 10 wk and were euthanatized at week 20 of the experiment. BBN was administered to male B6D2F₁ mice; it was either provided at a rate of 0.05% in the drinking water (for 26 wk) or 5 mg BBN was administered by intragastric gavage twice weekly for 10 wk, followed by 20 wk without treatment. In rats, BBN-induced, noninvasive, low-grade, papillary, transitional cell carcinoma (TCC) showed decreased uroplakin-staining of cells lining the lumen but showed increased expression in some nonluminal cells. In mice, nonpapillary, high-grade dysplasia, carcinoma in situ, and invasive carcinoma were induced. There was a marked decrease in the number of uroplakin-positive cells lining the lumen and in nonluminal cells. This occurred in normal-appearing urothelium in BBN-treated mice and in dysplasic urothelium, in carcinoma in situ, and in invasive TCC. The percentage of uroplakin-positive nonluminal cells was higher in control mice than in rats, but it was lower in the mouse than in the rat after BBN treatment. Uroplakin expression was disorderly and focal in BBN-treated urothelium in both species. These results indicate that BBN treatment changed the expression of uroplakins during bladder carcinogenesis, with differences in rats and mice being related to degree of tumor differentiation.

Key Words: Uroplakins • differentiation • bladder cancer • cell membranes

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