E-cadherin is regulated by the transcriptional repressor SLUG during Ras-mediated transformation of intestinal epithelial cells.
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.
Schmidt
Carl R
CR
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, USA.
Gi
Y J
YJ
Patel
Trusharth A
TA
Coffey
Robert J
RJ
Beauchamp
R Daniel
RD
Pearson
A Scott
AS
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
D015820:Cadherins; C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors