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Altered gene expression profile in mouse bladder cancers induced by hydroxybutyl(butyl)nitrosamine. Neoplasia 2004 Sep-Oct;6(5):569-77 PMID: 15548366 PMCID: PMC1531661

Pubmed ID

15548366

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, NFkappaB, and so on, in the TGF-beta signaling pathway and p115 RhoGEF, RhoGDI3, 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-beta pathways are involved, and the cross-talk between these pathways seems to play important roles in mouse bladder tumorigenesis.

Author List

Yao R, Lemon WJ, Wang Y, Grubbs CJ, Lubet RA, You M

Author

Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-6944225349   24 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Butylhydroxybutylnitrosamine
Down-Regulation
GTP-Binding Protein alpha Subunits, G12-G13
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Mice
Mice, Inbred Strains
Oligonucleotide Array Sequence Analysis
Signal Transduction
Transforming Growth Factor beta
Up-Regulation
Urinary Bladder Neoplasms
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e