Altered gene expression profile in mouse bladder cancers induced by hydroxybutyl(butyl)nitrosamine

Ruisheng Yao, William J. Lemon, Yian Wang, Clinton J. Grubbs, Ronald A. Lubet, Ming You

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A variety of genetic alterations and gene expression changes are involved in the pathogenesis of bladder tumor. To explore these changes, oligonucleotide array analysis was performed on RNA obtained from carcinogen-induced mouse bladder tumors and normal mouse bladder epithelia using Affymetrix (Santa Clara, CA) MGU74Av2 GeneChips. Analysis yielded 1164 known genes that were changed in the tumors. Certain of the upregulated genes included EGFR - Ras signaling genes, transcription factors, cell cycle - related genes, and intracellular signaling cascade genes. However, downregulated genes include mitogen-activated protein kinases, cell cycle checkpoint genes, Rab subfamily genes, Rho subfamily genes, and SH2 and SH3 domains - related genes. These genes are involved in a broad range of different pathways including control of cell proliferation, differentiation, cell cycle, signal transduction, and apoptosis. Using the pathway visualization tool GenMAPP, we found that several genes, including TbR-I, STAT1, Smad1, Smad2, Jun, NFκB, and so on, in the TGF-β signaling pathway and p115 RhoGEF, RhoGD13, MEKK4A/MEKK4B, PI3KA, and JNK in the G13 signaling pathway were differentially expressed in the tumors. In summary, we have determined the expression profiles of genes differentially expressed during mouse bladder tumorigenesis. Our results suggest that activation of the EGFR - Ras pathway, uncontrolled cell cycle, aberrant transcription factors, and G13 and TGF-β pathways are involved, and the cross-talk between these pathways seems to play important roles in mouse bladder tumorigenesis.

Original languageEnglish (US)
Pages (from-to)569-577
Number of pages9
JournalNeoplasia
Volume6
Issue number5
DOIs
StatePublished - 2004

Keywords

  • Affymetrix microarray
  • Differential expression
  • Expression profile
  • Mouse bladder cancer
  • Signaling pathway

ASJC Scopus subject areas

  • Cancer Research

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