title: E-cadherin is regulated by the transcriptional repressor SLUG during Ras-mediated transformation of intestinal epithelial cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, USA.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Schmidt
authors.forename: Y J
authors.initials: YJ
authors.lastname: Gi
authors.forename: Trusharth A
authors.initials: TA
authors.lastname: Patel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Beauchamp
authors.forename: A Scott
authors.initials: AS
authors.lastname: Pearson
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors