| Abstract: |
Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof. |
| Keywords: |
human tissue; unclassified drug; human cell; major clinical study; squamous cell carcinoma; carcinoma, squamous cell; pathophysiology; animals; mice; in situ hybridization, fluorescence; membrane proteins; cell differentiation; urinary bladder neoplasms; gene expression regulation; gene expression regulation, developmental; urothelium; gene expression regulation, neoplastic; amino acid sequence; molecular sequence data; sequence homology, amino acid; sequence alignment; membrane protein; urinary bladder; base sequence; cattle; retinol; carcinoma, transitional cell; malignant transformation; transitional cell carcinoma; polymorphism, genetic; chromosomes, human, pair 11; bladder carcinogenesis; chromosome 11q; polymorphism, single-stranded conformational; schistosomiasis; bladder epithelium; humans; human; priority journal; article; uroplakin 2
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