Document Detail

The use of two-dimensional gel electrophoresis in studies on the role of cytoskeletal plaque proteins as tumor suppressors.
MedLine Citation:
PMID:  8982608     Owner:  NLM     Status:  MEDLINE    
The morphology and functions of cells and tissues are determined, in a large part, by mechanical forces generated at cell-cell and cell-extracellular matrix (ECM) contacts. At these sites, transmembrane adhesion receptors of the integrin and cadherin families are linked, via their cytoplasmic domain, to the cytoskeleton by submembranal plaque proteins such as vinculin, alpha-actinin and the cell-cell junctional plaque proteins alpha- and beta-catenin and plakoglobin (or gamma-catenin). Recent studies have implicated this link of structural molecules between the outside and inside of the cell in signal transduction. We have shown that the expression of junctional plaque proteins is modulated during growth stimulation and differentiation, and is dramatically reduced in certain tumor cells. To study the functional significance of these changes in expression, we have used recombinant DNA technologies to overexpress or suppress the levels of junctional plaque proteins. In addition, we eliminated the expression of vinculin in embryonal stem (ES) cells and in the embryonal carcinoma F9 line by gene disruption employing homologous recombination. The results have indicated that moderate overexpression of cell-ECM plaque proteins results in reduced cell motility. In contrast, suppression of their expression, by antisense transfection, led to enhanced motility and conferred anchorage independent growth and tumorigenicity, upon injection into nude mice. These findings suggest that submembranal plaque proteins can act as effective tumor suppressors. In agreement with this notion, we found in several tumor cell lines diminished levels of junctional plaque proteins. Restoration of their level to that found in normal cells resulted in tumor suppression after their injection into experimental animals. Here we demonstrate the usefulness of the application of two dimensional (2-D) gel electrophoresis in these studies.
A Ben-Ze'ev
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Electrophoresis     Volume:  17     ISSN:  0173-0835     ISO Abbreviation:  Electrophoresis     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-05-29     Completed Date:  1997-05-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8204476     Medline TA:  Electrophoresis     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1752-63     Citation Subset:  IM    
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
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MeSH Terms
Actinin / biosynthesis,  genetics,  isolation & purification,  physiology
Adenocarcinoma / metabolism,  pathology
Carcinoma, Embryonal / metabolism,  pathology
Cell Adhesion
Cell Line, Transformed
Cell Transformation, Neoplastic
Cytoskeletal Proteins / isolation & purification*,  physiology
DNA, Complementary / genetics
Electrophoresis, Gel, Two-Dimensional*
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Intercellular Junctions / chemistry
Mice, Inbred BALB C
Microfilament Proteins / isolation & purification,  physiology
Neoplasm Proteins / biosynthesis,  genetics,  isolation & purification,  physiology
Neoplasm Transplantation
Pancreatic Neoplasms / metabolism,  pathology
Recombinant Fusion Proteins / metabolism
Simian virus 40 / physiology
Stem Cells / cytology,  metabolism
Tumor Cells, Cultured
Vinculin / biosynthesis,  genetics,  isolation & purification,  physiology
Reg. No./Substance:
0/Cytoskeletal Proteins; 0/DNA, Complementary; 0/Microfilament Proteins; 0/Neoplasm Proteins; 0/Recombinant Fusion Proteins; 11003-00-2/Actinin; 125361-02-6/Vinculin

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

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