Ogawa K, Sun T T, Cohen S M
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Carcinogenesis. 1996 May;17(5):961-5. doi: 10.1093/carcin/17.5.961.
Uroplakins are the major integral membrane proteins synthesized in terminally differentiated, superficial urothelial cells. Alteration of cell differentiation during rat urinary bladder carcinogenesis was analyzed immunohistochemically for the expression of uroplakins. Expression of uroplakins was compared in N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-, uracil-, sodium saccharin- or sodium ascorbate-induced urothelial simple hyperplasia, papillary-nodular hyperplasia, papilloma and carcinoma. In controls, uroplakins were located only in superficial cells, especially the luminal surface membrane. In FANFT-induced hyperplasia, including simple hyperplasia, intermediate cells also stained and the staining pattern was disorderly and intermittent. In uracil-induced simple hyperplasia, intermediate cells were stained but in an orderly fashion. In sodium saccharin- or sodium ascorbate-induced simple hyperplasia, superficial cells were swollen but alterations were not observed in the staining pattern. In carcinoma induced by FANFT and uracil, uroplakin expression was very disorderly and focal, usually with no expression on surface cells. It appears that disorderly differentiation is an index of bladder malignancy and is an early event in FANFT-induced lesions but a late event in uracil-, sodium saccharin- and sodium ascorbate-induced lesions.
uroplakins是在终末分化的表层尿路上皮细胞中合成的主要整合膜蛋白。通过免疫组织化学分析大鼠膀胱癌发生过程中细胞分化的改变，以检测uroplakins的表达。比较了N-[4-(5-硝基-2-呋喃基)-2-噻唑基]-甲酰胺（FANFT）、尿嘧啶、糖精钠或抗坏血酸钠诱导的尿路上皮单纯性增生、乳头状-结节状增生、乳头状瘤和癌中uroplakins的表达。在对照组中，uroplakins仅位于表层细胞，尤其是腔面膜。在FANFT诱导的增生中，包括单纯性增生，中间细胞也有染色，且染色模式紊乱且间断。在尿嘧啶诱导的单纯性增生中，中间细胞有染色，但染色有序。在糖精钠或抗坏血酸钠诱导的单纯性增生中，表层细胞肿胀，但染色模式未观察到改变。在FANFT和尿嘧啶诱导的癌中，uroplakin表达非常紊乱且呈局灶性，通常表层细胞无表达。似乎分化紊乱是膀胱恶性肿瘤的一个指标，在FANFT诱导的病变中是早期事件，而在尿嘧啶、糖精钠和抗坏血酸钠诱导的病变中是晚期事件。
