Document Detail


beta-catenin (CTNNB1) gene amplification: a new mechanism of protein overexpression in cancer.
MedLine Citation:
PMID:  15609344     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
beta-Catenin nuclear translocation is frequently observed in different types of malignancies, including gastric cancer. In gastric cancer, however, the molecular mechanisms leading to accumulation of this protein in the nucleus remain unknown. In this setting, beta-catenin (CTNNB1) mutations have been reported, but studies of mutation frequency have yielded conflicting results. Mutations or silencing of other partners of beta-catenin (i.e., APC and AXIN) are also considered rare genetic events in gastric tumorigenesis. Gene amplification is a common mechanism of activation and/or overexpression of oncogenes in gastric and other cancers. In this study, we investigated whether gene amplification is a possible mechanism of beta-catenin activation in gastric cancer by determining its presence in 49 patients with gastric cancer and two gastric-derived cell lines (KATO III and ST2957). Using fluorescence in situ hybridization, we identified beta-catenin amplification in one of the tumor samples as well as in KATO III cells. beta-Catenin immunostaining revealed nuclear translocation of the protein in both cases. In the KATO III cells, beta-catenin overexpression was confirmed by quantitative real-time PCR and Western blot analyses and beta-catenin gene amplification by Southern blot analysis and multiplex ligation probe amplification. In the KATO III cell line, no correlation was found between beta-catenin nuclear translocation and increased expression of the WNT1 target gene CCND1 (cyclin D1). Our data suggest that gene amplification is a possible mechanism of beta-catenin overexpression in cancer.
Authors:
Gianpaolo Suriano; Nikoleta Vrcelj; Janine Senz; Paulo Ferreira; Hamid Masoudi; Kelley Cox; Sergio Nabais; Carlos Lopes; José Carlos Machado; Raquel Seruca; Fatima Carneiro; David G Huntsman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  42     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-01-17     Completed Date:  2005-05-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  238-46     Citation Subset:  IM    
Affiliation:
Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Centre at Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency and University of British Columbia, Vancouver, Canada.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Southern
Blotting, Western
Cell Nucleus / genetics,  metabolism*
Cyclin D1 / metabolism
Cytoskeletal Proteins / genetics*,  metabolism
DNA Mutational Analysis
Exons / genetics
Gene Amplification*
Gene Deletion
Gene Expression Regulation, Neoplastic*
Humans
In Situ Hybridization, Fluorescence
Intestinal Neoplasms / genetics,  metabolism,  pathology
Mutation
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / genetics*,  metabolism,  pathology
Trans-Activators / genetics*,  metabolism
Tumor Cells, Cultured
Up-Regulation
beta Catenin
Chemical
Reg. No./Substance:
0/CTNNB1 protein, human; 0/Cytoskeletal Proteins; 0/Trans-Activators; 0/beta Catenin; 136601-57-5/Cyclin D1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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