Robert Beauchamp
Principal Investigator
Last active: 10/31/2018

Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is blocked by inhibiting MAP kinase.

Schmidt CR, Washington MK, Gi YJ, Coffey RJ, Beauchamp RD, Pearson AS
Am J Surg. 2003 186 (5): 426-30

PMID: 14599601 · DOI:10.1016/j.amjsurg.2003.07.004

BACKGROUND - Mutations in oncogenic Ras contribute to colorectal tumorigenesis. Loss of the cell adhesion protein E-cadherin is associated with tumor invasion and metastasis.

METHODS - Expression of oncogenic Ras was induced in intestinal epithelial cells. Changes in cell morphology, E-cadherin protein expression, and E-cadherin localization were examined by light microscopy, Western blot, and immunofluorescence respectively. Expression of E-cadherin in human colorectal tumors was examined by immunohistochemistry.

RESULTS - Induction of oncogenic Ras results in an epithelial to mesenchymal transformation with loss of membranous E-cadherin expression and mis-localization to the cytoplasm. Removal of Ras stimulus or blockade of the MAP kinase pathway allowed reversion to a normal cellular phenotype and return of E-cadherin to the cell membrane. Loss of or decreased expression of E-cadherin was observed in seven of eight colorectal tumors.

CONCLUSIONS - Oncogenic Ras contributes to malignant transformation and altered E-cadherin expression in intestinal epithelial cells. Similar dysregulation of E-cadherin is found in human colorectal tumors. Ras effects on E-cadherin are critical to malignant transformation in our in-vitro model and may be an important event in human colorectal tumors.

MeSH Terms (15)

Animals Blotting, Western Butadienes Cadherins Cells, Cultured Colorectal Neoplasms Enzyme Inhibitors Epithelial Cells Genes, ras Humans Intestinal Mucosa Mitogen-Activated Protein Kinase Kinases Mutation Nitriles Rats

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