A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions

TY - JOUR

T1 - A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions

AU - Perez-Moreno, M A

AU - Locascio, A

AU - Rodrigo, I

AU - Dhondt, G

AU - Portillo, F

AU - Nieto, M A

AU - Cano, A

PY - 2001/7/20

Y1 - 2001/7/20

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

SN - 0021-9258

VL - 276

SP - 27424

EP - 27431

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 29

ER -