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Human disc large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissues architecture during malignant progression
- Publication Year :
- 2006
-
Abstract
- Loss of cell polarity is one of the hallmarks of malignant carcinomas. Most of the understanding about the link between cell polarity and proliferation control comes from studies on the Drosophila tumor suppressors discs large (Dlg), scribble (Scrib) and lethal giant larvae (lgl). Mammalian homologues of these proteins have been described and are conserved in sequence and function. Human Dlg (hDlg) and Scrib were independently shown to be down-regulated during malignant progression. This, and other lines of evidence, points toward the participation of both hDlg and hScrib in a common pathway involved in polarity control and tumor suppression. We investigated the correlation between the expression of both proteins in tissues and their relative contributions to the maintenance of tissue architecture during colon cancer development. We analyzed the levels and distribution of hDlg and hScrib by immunohistochemistry, using serial sections of the same sample. We used normal and neoplastic colon mucosa, since it offers a good model for analyzing these features in progressive dysplastic stages. The results demonstrate that both proteins localize at the same regions in polarized colon epithelia, and that in normal samples the proteins' distribution varies as cells differentiate at the surface mucosa. In neoplasia, alterations in the expression pattern of hDlg and of hScrib increase during tumor progression; down-regulation of both proteins being associated with lack of epithelial cell polarity and disorganized tissue architecture. The results, therefore, demonstrate that there is an inverse relationship between the levels of hDlg and hScrib expression and the loss of cell polarity and tissue architecture in the colon. © 2006 Wiley-Liss, Inc.
- Subjects :
- SCRIB
Cancer Research
Pathology
medicine.medical_specialty
Tumor suppressor gene
Colon
Biology
Adenocarcinoma
medicine.disease_cause
Malignant transformation
Discs Large Homolog 1 Protein
Cell polarity
medicine
Humans
Intestinal Mucosa
Epithelial polarity
Adaptor Proteins, Signal Transducing
hDlg
Tumor Suppressor Proteins
Cell Polarity
Membrane Proteins
Cell Differentiation
colon cancer
tissue architecture
Scribble tumor suppressors
Cell biology
Oncology
Tumor progression
Colonic Neoplasms
Disease Progression
Immunohistochemistry
Carcinogenesis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....90eb51f4d9d2519cd04b86ae89cda6b4