Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models.
Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB and Tcf-4 are often found in human cancers including colorectal cancer (CRC) and have been implicated in the development and progression of tumorigenesis. The aim of this study was to determine the expression of these genes in mouse models of sporadic and colitis-associated CRC. To address these issues, we used qRT-PCR approach to determine changes in gene expression patterns of neoplastic cells (high-grade dysplasia/intramucosal carcinoma) and surrounding normal epithelial cells in A/J and ICR mouse strains using laser microdissection. Both strains were injected with azoxymethane and ICR mice were also given drinking water that contained 2% dextran sodium sulphate. In both sporadic (A/J mice) and colitis-associated (ICR mice) models of CRC, the levels of TERT mRNA, COX-2 mRNA and Tcf-4 mRNA were higher in neoplastic cells than in surrounding normal epithelial cells. In contrast, survivin mRNA was upregulated only in neoplastic cells from A/J mice and ILK mRNA was upregulated only in neoplastic cells from ICR mice. However, the expression of iNOS mRNA was similar in normal and neoplastic cells in both models and c-MYB mRNA was actually downregulated in neoplastic cells compared with normal cells in both models. These findings suggest that the genetic background and/or the molecular mechanisms of tumorigenesis associated with genotoxic insults and colonic inflammation influence the gene expression of mTERT, COX-2, Tcf-4, c-MYB, ILK and survivin in colon epithelial neoplasia.
Svec
Jirí
J
Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Ergang
Peter
P
Mandys
Václav
V
Kment
Milan
M
Pácha
Jirí
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001397:Azoxymethane; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D042282:Microdissection; D008869:Microtubule-Associated Proteins / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D019098:Telomerase / Q000235:genetics; D000073940:Transcription Factor 4; D000099200:Scaffold Protein ILK
D051017:Apoptosis Regulatory Proteins; D001397:Azoxymethane; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D051546:Cyclooxygenase 2; D016264:Dextran Sulfate; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D000077022:Survivin; D019098:Telomerase; D000073940:Transcription Factor 4; D000099200:Scaffold Protein ILK; C117749:Birc5 protein, mouse; C090743:Tcf4 protein, mouse; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; C509187:Tert protein, mouse