Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer

Farhad Vesuna, Paulus Joannes van Diest, Ji Hshiung Chen, Venu Raman

Research output: Contribution to journalArticlepeer-review

Abstract

Twist is a basic helix loop helix protein that plays a role both in human development and in cancer biogenesis. While characterizing the effects of Twist on breast epithelial cell transformation, we identified E-cadherin as a target gene that is down-regulated by Twist. In this study, we demonstrate that Twist can transcriptionally repress E-cadherin in breast cancer cells. Using transient promoter assays, we show that Twist can down-regulate E-cadherin promoter activity by up to two folds. This is further supported by immunoblot analyses which indicates that over-expression of Twist decreases E-cadherin protein levels in breast cancer cell lines. Subsequently, chromatin immunoprecipitation performed on MCF-7/Twist and Hs578 T (high level of endogenous Twist expression) confirmed Twist binding to the E-cadherin promoter. Finally, the functional relevance of this regulation was verified by quantitative real-time PCR and immunohistochemistry on a cohort of breast cancer samples.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number2
DOIs
StatePublished - Mar 7 2008

Keywords

  • Breast cancer
  • E-cadherin
  • Transcription regulation
  • Twist

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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