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

Marta Sanchez-Carbayo, Nicholas D. Socci, Elizabeth Charytonowicz, Minglan Lu, Michael B. Prystowsky, Geoffrey J. Childs, Carlos Cordon-Cardo

Research output: Contribution to journalArticle

160 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6973-6980
Number of pages8
JournalCancer Research
Volume62
Issue number23
StatePublished - Dec 1 2002

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Oligonucleotide Array Sequence Analysis
Urinary Bladder Neoplasms
Phenotype
Cell Cycle
Cell Adhesion
Cluster Analysis
Neoplasms
Zyxin
Keratin-10
Cyclin-Dependent Kinase Inhibitor p16
Caveolin 1
Cell Line
Expressed Sequence Tags
Cadherins
Tumor Cell Line
Genes
Epithelial Cells
Immunohistochemistry
Mutation
moesin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sanchez-Carbayo, M., Socci, N. D., Charytonowicz, E., Lu, M., Prystowsky, M. B., Childs, G. J., & Cordon-Cardo, C. (2002). Molecular profiling of bladder cancer using cDNA microarrays: Defining histogenesis and biological phenotypes. Cancer Research, 62(23), 6973-6980.

Molecular profiling of bladder cancer using cDNA microarrays : Defining histogenesis and biological phenotypes. / Sanchez-Carbayo, Marta; Socci, Nicholas D.; Charytonowicz, Elizabeth; Lu, Minglan; Prystowsky, Michael B.; Childs, Geoffrey J.; Cordon-Cardo, Carlos.

In: Cancer Research, Vol. 62, No. 23, 01.12.2002, p. 6973-6980.

Research output: Contribution to journalArticle

Sanchez-Carbayo, M, Socci, ND, Charytonowicz, E, Lu, M, Prystowsky, MB, Childs, GJ & Cordon-Cardo, C 2002, 'Molecular profiling of bladder cancer using cDNA microarrays: Defining histogenesis and biological phenotypes', Cancer Research, vol. 62, no. 23, pp. 6973-6980.
Sanchez-Carbayo, Marta ; Socci, Nicholas D. ; Charytonowicz, Elizabeth ; Lu, Minglan ; Prystowsky, Michael B. ; Childs, Geoffrey J. ; Cordon-Cardo, Carlos. / Molecular profiling of bladder cancer using cDNA microarrays : Defining histogenesis and biological phenotypes. In: Cancer Research. 2002 ; Vol. 62, No. 23. pp. 6973-6980.
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