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.
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Authors | R L Wu, I Osman, X R Wu, M L Lu, Z F Zhang, F X Liang, R Hamza, H Scher, C Cordon-Cardo, T T Sun |
Journal | Cancer research
(Cancer Res)
Vol. 58
Issue 6
Pg. 1291-7
(Mar 15 1998)
ISSN: 0008-5472 [Print] United States |
PMID | 9515818
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Membrane Proteins
- UPK2 protein, human
- Upk2 protein, mouse
- Uroplakin II
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Topics |
- Amino Acid Sequence
- Animals
- Base Sequence
- Carcinoma, Squamous Cell
(genetics)
- Carcinoma, Transitional Cell
(genetics)
- Cattle
- Cell Differentiation
- Chromosomes, Human, Pair 11
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Neoplastic
- Humans
- In Situ Hybridization, Fluorescence
- Membrane Proteins
(genetics)
- Mice
- Molecular Sequence Data
- Polymorphism, Genetic
- Polymorphism, Single-Stranded Conformational
- Schistosomiasis
(complications)
- Sequence Alignment
- Sequence Homology, Amino Acid
- Urinary Bladder
(physiology)
- Urinary Bladder Neoplasms
(genetics)
- Uroplakin II
- Urothelium
(physiology)
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