title: Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.
abstract: Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression.
authors.affiliation: New England Deaconess Hospital, Department of Surgery, Harvard Medical School, Boston, Massachussetts 02115, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Rieger
authors.forename: A F
authors.initials: AF
authors.lastname: Little
authors.forename: J M
authors.initials: JM
authors.lastname: Swart
authors.forename: W V
authors.initials: WV
authors.lastname: Kastrinakis
authors.forename: J M
authors.initials: JM
authors.lastname: Fitzgerald
authors.forename: D T
authors.initials: DT
authors.lastname: Hess
authors.forename: J A
authors.initials: JA
authors.lastname: Libertino
authors.forename: I C
authors.initials: IC
authors.lastname: Summerhayes
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2