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

@article{citeulike:887296, abstract = {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.}, address = {Department of Surgery, Vanderbilt University Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.}, author = {Schmidt, C. R. and Washington, M. K. and Gi, Y. J. and Coffey, R. J. and Beauchamp, R. D. and Pearson, A. S.}, citeulike-article-id = {887296}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/14599601}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=14599601}, issn = {0002-9610}, journal = {Am J Surg}, keywords = {e-cadherin, emt, k-ras}, month = {November}, number = {5}, pages = {426--430}, posted-at = {2006-10-06 14:06:20}, priority = {2}, title = {Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is blocked by inhibiting MAP kinase.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14599601}, volume = {186}, year = {2003} }

TY - JOUR ID - citeulike:887296 L3 - citeulike-article-id:887296 N2 - 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. IS - 5 JF - Am J Surg SN - 0002-9610 AD - Department of Surgery, Vanderbilt University Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. EP - 430 TI - Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is blocked by inhibiting MAP kinase. VL - 186 SP - 426 KW - e-cadherin KW - emt KW - k-ras AU - Schmidt, CR AU - Washington, MK AU - Gi, YJ AU - Coffey, RJ AU - Beauchamp, RD AU - Pearson, AS PY - 2003/11// UR - http://view.ncbi.nlm.nih.gov/pubmed/14599601 ER -