Altered gene expression profile in mouse bladder cancers induced by hydroxybutyl(butyl)nitrosamine.
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.
Yao
Ruisheng
R
Department of Surgery and The Alvin J. Siteman Cancer Center, Campus Box 8109, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lemon
William J
WJ
Wang
Yian
Y
Grubbs
Clinton J
CJ
Lubet
Ronald A
RA
You
Ming
M
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000494:pharmacology*; D015536:Down-Regulation / Q000235:genetics; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
D016212:Transforming Growth Factor beta; D002085:Butylhydroxybutylnitrosamine; D044365:GTP-Binding Protein alpha Subunits, G12-G13