Ogawa K, St John M, Luiza de Oliveira M, Arnold L, Shirai T, Sun T T, Cohen S M
Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Toxicol Pathol. 1999 Nov-Dec;27(6):645-51. doi: 10.1177/019262339902700606.
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 B6D2F, 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.
尿路上皮特异且依赖分化的膜蛋白uroplakins的表达，在N-丁基-N-(4-羟基丁基)亚硝胺（BBN）处理的大鼠和小鼠膀胱癌发生过程中，通过免疫组织化学方法进行了分析。雄性Fischer 344大鼠饮用含0.05%BBN的水10周，并在实验第20周时安乐死。雄性B6D2F1小鼠接受BBN处理；要么以0.05%的比例添加到饮用水中（持续26周），要么每周两次通过灌胃给予5mg BBN，持续10周，随后20周不进行处理。在大鼠中，BBN诱导的非侵袭性、低级别、乳头状移行细胞癌（TCC）显示管腔衬里细胞的uroplakin染色减少，但在一些非管腔细胞中表达增加。在小鼠中，诱导出了非乳头状、高级别发育异常、原位癌和浸润性癌。管腔衬里和非管腔的uroplakin阳性细胞数量显著减少。这发生在BBN处理小鼠外观正常的尿路上皮、发育异常的尿路上皮、原位癌和浸润性TCC中。对照小鼠中uroplakin阳性非管腔细胞的百分比高于大鼠，但BBN处理后小鼠中的该百分比低于大鼠。在两个物种中经BBN处理的尿路上皮中，uroplakin表达均紊乱且呈局灶性。这些结果表明，BBN处理在膀胱癌发生过程中改变了uroplakins的表达，大鼠和小鼠的差异与肿瘤分化程度有关。
