Document Detail

Changes in expression of the human homologue of the Drosophila discs large tumour suppressor protein in high-grade premalignant cervical neoplasias.
MedLine Citation:
PMID:  12419826     Owner:  NLM     Status:  MEDLINE    
The Drosophila tumour suppressor discs large (Dlg) is a cell-junction localized protein that is required for the maintenance of epithelial cyto-architecture and the negative control of cell proliferation. The mammalian homologue is likely to have a similar mode of action, and therefore functional perturbation of this protein may be linked to the development of epithelial-derived cancers. The finding that several unrelated viral oncoproteins, including the E6 protein of oncogenic human papillomaviruses, bind to the human homologue of Dlg (hDlg) supports this proposition. Employing immunohistochemistry, we show that in uterine cervical squamous epithelia, prominent localization of hDlg at sites of intercellular contact occurs in cells that have left the proliferating basal cell layers and begun maturation. The presence of hDlg at sites of cell:cell contact diminishes, whilst intracellular cytoplasmic levels increase significantly in high-grade, but not low-grade, cervical neoplasias. In invasive squamous cell carcinomas, total cellular hDlg levels are greatly reduced. Our data suggest that loss of hDlg at sites of intercellular contact may be an important step in the development of epithelial cancers.
Richard A Watson; Terry P Rollason; Gary M Reynolds; Paul G Murray; Lawrence Banks; Sally Roberts
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  23     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-06     Completed Date:  2002-12-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1791-6     Citation Subset:  IM    
Cancer Research UK Institute for Cancer Studies, The Medical School, University of Birmingham, UK.
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MeSH Terms
Adaptor Proteins, Signal Transducing
Antibodies, Monoclonal / immunology
Carcinoma, Squamous Cell / chemistry,  genetics*,  pathology
Cell Adhesion
Cell Compartmentation
Cervical Intraepithelial Neoplasia / chemistry,  genetics*,  pathology
Cervix Uteri / chemistry
Cytoplasm / chemistry
Epithelial Cells / chemistry
Gene Expression Regulation, Neoplastic*
Genes, Tumor Suppressor*
Membrane Proteins
Neoplasm Invasiveness
Neoplasm Proteins / biosynthesis*,  genetics,  immunology
Protein Biosynthesis*
Proteins / genetics,  immunology
Uterine Cervical Dysplasia / metabolism,  pathology
Uterine Cervical Neoplasms / chemistry,  genetics*,  pathology
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antibodies, Monoclonal; 0/DLG1 protein, human; 0/Membrane Proteins; 0/Neoplasm Proteins; 0/Proteins

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