A New Role for E12/E47 in the Repression of E-cadherin Expression and Epithelial-Mesenchymal Transitions
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A New Role for E12/E47 in the Repression of E-cadherin Expression and Epithelial-Mesenchymal Transitions. / Pérez-Moreno, Mirna A.; Locascio, Annamaria; Rodrigo, Isabel; Dhondt, Goedele; Portillo, Francisco; Nieto, M. Angela; Cano, Amparo.
I: The Journal of Biological Chemistry, Bind 276, Nr. 29, 2001, s. 27424-27431.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A New Role for E12/E47 in the Repression of E-cadherin Expression and Epithelial-Mesenchymal Transitions
AU - Pérez-Moreno, Mirna A.
AU - Locascio, Annamaria
AU - Rodrigo, Isabel
AU - Dhondt, Goedele
AU - Portillo, Francisco
AU - Nieto, M. Angela
AU - Cano, Amparo
PY - 2001
Y1 - 2001
N2 - Down-regulation of E-cadherin expression is a determinant of tumor cell invasiveness, an event frequently associated with epithelial-mesenchymal transitions. Here we show that the mouse E12/E47 basic helix-loop-helix transcription factor (the E2A gene product) acts as a repressor of E-cadherin expression and triggers epithelial-mesenchymal transitions. The mouse E47 factor was isolated in a one-hybrid system designed to isolate repressors of the mouse E-cadherin promoter. Epithelial cells ectopically expressing E47 adopt a fibroblastic phenotype and acquire tumorigenic and migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Suppression of E-cadherin expression under stable or inducible expression of E47 in epithelial cells occurs at the transcriptional level and is dependent on the E-boxes of the E-cadherin promoter. Interestingly, analysis of endogenous E2A expression in murine and human cell lines illustrated its presence in E-cadherin-deficient, invasive carcinoma cells but its absence from epithelial cell lines. This expression pattern is consistent with that observed in early mouse embryos, where E2A mRNA is absent from epithelia but strongly expressed in the mesoderm. These results implicate E12/E47 as a repressor of E-cadherin expression during both development and tumor progression and indicate its involvement in the acquisition and/or maintenance of the mesenchymal phenotype.
AB - Down-regulation of E-cadherin expression is a determinant of tumor cell invasiveness, an event frequently associated with epithelial-mesenchymal transitions. Here we show that the mouse E12/E47 basic helix-loop-helix transcription factor (the E2A gene product) acts as a repressor of E-cadherin expression and triggers epithelial-mesenchymal transitions. The mouse E47 factor was isolated in a one-hybrid system designed to isolate repressors of the mouse E-cadherin promoter. Epithelial cells ectopically expressing E47 adopt a fibroblastic phenotype and acquire tumorigenic and migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Suppression of E-cadherin expression under stable or inducible expression of E47 in epithelial cells occurs at the transcriptional level and is dependent on the E-boxes of the E-cadherin promoter. Interestingly, analysis of endogenous E2A expression in murine and human cell lines illustrated its presence in E-cadherin-deficient, invasive carcinoma cells but its absence from epithelial cell lines. This expression pattern is consistent with that observed in early mouse embryos, where E2A mRNA is absent from epithelia but strongly expressed in the mesoderm. These results implicate E12/E47 as a repressor of E-cadherin expression during both development and tumor progression and indicate its involvement in the acquisition and/or maintenance of the mesenchymal phenotype.
KW - Animals
KW - Base Sequence
KW - Cadherins
KW - Cell Line
KW - DNA Primers
KW - DNA-Binding Proteins
KW - Dogs
KW - Down-Regulation
KW - Epithelium
KW - Mesoderm
KW - Mice
KW - Molecular Sequence Data
KW - Protein Binding
KW - Recombinant Proteins
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - TCF Transcription Factors
KW - Transcription Factor 7-Like 1 Protein
KW - Transcription Factors
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1074/jbc.M100827200
DO - 10.1074/jbc.M100827200
M3 - Journal article
C2 - 11309385
VL - 276
SP - 27424
EP - 27431
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 29
ER -
ID: 188406954