Molecular profiling of bladder cancer using cDNA microarrays: Defining histogenesis and biological phenotypes Journal Article


Authors: Sanchez Carbayo, M.; Socci, N. D.; Charytonowicz, E.; Lu, M.; Prystowsky, M.; Childs, G.; Cordon-Cardo, C.
Article Title: Molecular profiling of bladder cancer using cDNA microarrays: Defining histogenesis and biological phenotypes
Abstract: This study was designed to characterize the expression profiles of nine bladder cancer cell lines (T24, J82, 5637, HT1376, RT4, SCaBER, TCCSUP, UMUC-3, and HT1197) using cDNA microarrays (8976 genes and expressed sequence tags). Novel targets involved in bladder cancer progression of potential clinical relevance were validated by immunohistochemistry using tissue microarrays of primary bladder tumors (n = 193 cases). Hierarchical clustering classified uroepithelial cells based on their histopathogenesis and cell cycle alterations. Keratin 10 and caveolin-1 transcripts were more abundant in tumor cells from squamous and invasive origin. Their combined expression was shown to stratify bladder tumors and define squamous differentiation. To assess the robustness of the clustering analysis, a bootstrap resampling technique was used. This grouped tumor cell lines based on their biological properties, including cell cycle and cell adhesion features. E-cadherin, zyxin, and moesin were identified as genes differentially expressed in these clusters and related to the p53, RB, and INK4A status of the cell lines. Loss of these adhesion molecules was associated with stage and grade in primary tumors (P < 0.05), and moesin expression was also associated with survival (P = 0.01). Deregulation of cell cycle and apoptotic pathways, such as mutations or altered expression of p53, pRB, and INK4A (p16), is necessary for uroepithelial transformation. However, it appears that deregulation of cell adhesion is a common event associated with tumor progression in uroepithelial neoplasms.
Keywords: immunohistochemistry; controlled study; unclassified drug; gene cluster; gene mutation; human cell; histopathology; carcinoma, squamous cell; cancer growth; validation process; cancer staging; neoplasm staging; phenotype; cell cycle; apoptosis; cluster analysis; gene expression; gene expression profiling; tumor markers, biological; cell differentiation; tumor cells, cultured; microfilament proteins; bladder cancer; protein p53; uvomorulin; urinary bladder neoplasms; oligonucleotide array sequence analysis; expressed sequence tag; gene identification; epithelium cell; tumor suppressor protein p53; dna microarray; keratins; carcinoma, transitional cell; retinoblastoma protein; cell adhesion; cadherins; glycoproteins; monte carlo method; moesin; cytoskeletal proteins; histogenesis; keratin; deregulation; metalloproteins; zyxin; caveolin 1; humans; prognosis; human; priority journal; article; keratin 10; caveolins; keratin-10
Journal Title: Cancer Research
Volume: 62
Issue: 23
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2002-12-01
Start Page: 6973
End Page: 6980
Language: English
PUBMED: 12460915
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact