E-cadherin is a WT1 target gene

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Published on: October 27, 2014

S Hosono1, I Gross, M A English

  • 1Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.

The Journal of Biological Chemistry
|February 7, 2001
PubMed

Insights

The WT1 tumor suppressor gene promotes epithelial differentiation and growth suppression by up-regulating E-cadherin. This study identifies E-cadherin as a key downstream target linking WT1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The WT1 (Wilms Tumor 1) gene is a tumor suppressor.
  • WT1's role in growth suppression is linked to its transcriptional targets, which are not fully understood.
  • WT1's function in differentiation and growth control needs further elucidation.

Purpose of the Study:

  • To identify downstream target genes of WT1.
  • To investigate the role of WT1 in epithelial differentiation.
  • To understand the mechanism by which WT1 regulates E-cadherin.

Main Methods:

  • Stable and acute expression of WT1 in NIH 3T3 fibroblasts.
  • Retroviral infection for gene expression.
  • Transient transfection assays to analyze promoter activity.
  • In vitro binding assays to study protein-DNA interactions.

Main Results:

  • WT1 expression induced growth suppression and epithelial differentiation features, including E-cadherin upregulation.
  • WT1 activated both human and murine E-cadherin promoters.
  • WT1 bound to a specific response element in the murine E-cadherin promoter.

Conclusions:

  • E-cadherin is a downstream target gene of WT1.
  • WT1 links epithelial differentiation and growth control through E-cadherin regulation.
  • WT1's function in tumor suppression may involve modulating E-cadherin expression.

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