title: Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation.
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.
authors.affiliation: The Ronald Perelman Department of Dermatology, New York University Medical School, New York 10016, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Wu
authors.forename: I
authors.initials: I
authors.lastname: Osman
authors.forename: X R
authors.initials: XR
authors.lastname: Wu
authors.forename: M L
authors.initials: ML
authors.lastname: Lu
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: F X
authors.initials: FX
authors.lastname: Liang
authors.forename: R
authors.initials: R
authors.lastname: Hamza
authors.forename: H
authors.initials: H
authors.lastname: Scher
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: T T
authors.initials: TT
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002417:Cattle; D002454:Cell Differentiation; D002880:Chromosomes, Human, Pair 11; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012552:Schistosomiasis / Q000150:complications*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D001743:Urinary Bladder / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D060170:Uroplakin II; D019459:Urothelium / Q000502:physiology
chemical_list: D008565:Membrane Proteins; C554658:UPK2 protein, human; C554659:Upk2 protein, mouse; D060170:Uroplakin II