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E-cadherin is regulated by the transcriptional repressor SLUG during Ras-mediated transformation of intestinal epithelial cells.

Schmidt CR, Gi YJ, Patel TA, Coffey RJ, Beauchamp RD, Pearson AS
Surgery. 2005 138 (2): 306-12

PMID: 16153441 · DOI:10.1016/j.surg.2005.06.007

BACKGROUND - Loss of the cell membrane protein E-cadherin is a critical event during Ras-mediated transformation of intestinal epithelial cells. The purpose of our study is to determine if activation of the transcriptional repressor SLUG is an important component of the mechanism of Ras-induced loss of E-cadherin.

METHODS - Rat intestinal epithelial (RIE) cells were engineered to express mutated human Ha-Ras(Val12) complementary DNA (H-Ras cells). Cell morphology was examined by light microscopy. RNA and protein expression were measured by semiquantitative polymerase chain reaction and Western blot analyses, respectively. Short interfering RNA with 2 different oligos was used to knock down the expression of SLUG.

RESULTS - Oncogenic ras induces upregulation of the transcriptional repressor SLUG and subsequent downregulation of the junctional protein E-cadherin. Gene silencing of SLUG by short interfering RNA allows E-cadherin to be reexpressed. E-cadherin protein reexpression allows partial rescue of the transformed phenotype.

CONCLUSION - These data suggest a mechanism whereby Ras signaling causes an upregulation of transcriptional repressors and subsequent downregulation of E-cadherin as a malignant phenotype is propagated.

MeSH Terms (13)

Animals Cadherins Cell Line Cell Transformation, Neoplastic Down-Regulation Gene Expression Regulation, Neoplastic Genes, ras Intestinal Mucosa Phenotype Rats Snail Family Transcription Factors Transcription, Genetic Transcription Factors

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