Document Detail


Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models.
MedLine Citation:
PMID:  20096072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jirí Svec; Peter Ergang; Václav Mandys; Milan Kment; Jirí Pácha
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of experimental pathology     Volume:  91     ISSN:  1365-2613     ISO Abbreviation:  Int J Exp Pathol     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-25     Completed Date:  2010-02-04     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  9014042     Medline TA:  Int J Exp Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  44-53     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics*
Apoptosis Regulatory Proteins / genetics*
Azoxymethane
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
Cell Cycle Proteins / genetics*
Cell Proliferation*
Cell Transformation, Neoplastic / chemically induced,  genetics
Colitis / chemically induced,  complications,  genetics*,  pathology
Colonic Neoplasms / chemically induced,  genetics*,  pathology
Cyclooxygenase 2 / genetics
Dextran Sulfate
Disease Models, Animal
Disease Progression
Gene Expression Profiling* / methods
Gene Expression Regulation, Neoplastic*
Inhibitor of Apoptosis Proteins
Male
Mice
Mice, Inbred ICR
Microdissection
Microtubule-Associated Proteins / genetics
Nitric Oxide Synthase Type II / genetics
Protein-Serine-Threonine Kinases / genetics
Proto-Oncogene Proteins c-myb / genetics
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / genetics
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/Birc5 protein, mouse; 0/Cell Cycle Proteins; 0/Inhibitor of Apoptosis Proteins; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Repressor Proteins; 0/Tcf4 protein, mouse; 25843-45-2/Azoxymethane; 9042-14-2/Dextran Sulfate; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 2; EC 2.7.1.-/integrin-linked kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse
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