Journal Article

Changes in expression of the human homologue of the <i>Drosophila</i> discs large tumour suppressor protein in high-grade premalignant cervical neoplasias

Richard A. Watson, Terry P. Rollason, Gary M. Reynolds, Paul G. Murray, Lawrence Banks and Sally Roberts

in Carcinogenesis

Volume 23, issue 11, pages 1791-1796
Published in print November 2002 | ISSN: 0143-3334
Published online November 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.11.1791
Changes in expression of the human homologue of the Drosophila discs large tumour suppressor protein in high-grade premalignant cervical neoplasias

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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.

Keywords: APC, adenomatous polyposis coli; CIN, cervical intraepithelial neoplasia; Dlg, Drosophila tumour suppressor discs large; hDlg, human homologue of Dlg; HPV, human papilloma virus; MAGUK, membrane-associated guanylate kinase; SIL, squamous intraepithelial lesions

Journal Article.  4136 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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