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Related Experiment Videos

Ets up-regulates MET transcription

G Gambarotta1, C Boccaccio, S Giordano

  • 1Institute for Cancer Research, University of Torino Medical School, Italy.

Oncogene
|November 7, 1996
PubMed
Summary

The Ets transcription factor family enhances MET oncogene transcription, contributing to cancer

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Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The MET oncogene drives invasive cancer growth and is overexpressed in many human cancers.
  • Gene amplification explains MET overexpression in only a subset of cases, necessitating investigation into transcriptional regulation.

Purpose of the Study:

  • To elucidate the transcriptional mechanisms responsible for MET oncogene up-regulation.
  • To identify specific DNA elements and transcription factors that control MET promoter activity.

Main Methods:

  • 5' progressive deletion analysis of the MET promoter region (3.1 kbp).
  • Transient co-expression assays with Ets1 transcription factor.
  • Stable transfection studies with ETS1.
  • Oligonucleotide 'decoy' experiments to inhibit Ets binding.

Main Results:

  • The region within 300 bp upstream of the MET transcription start site strongly up-regulates promoter activity.
  • This region contains putative Ets transcription factor binding sites, and Ets1 co-expression enhances MET promoter activity.
  • Ets binding inhibition via decoy oligonucleotides significantly reduced Met protein levels in carcinoma cells.
  • Met activation was found to induce ETS1 mRNA transcription, indicating a feedback loop.

Conclusions:

  • Members of the Ets transcription factor family play a crucial role in promoting MET transcription.
  • Ets proteins contribute to the invasive cancer phenotype through the overexpression of MET.
  • A positive feedback loop exists where Met activation induces ETS1 transcription.

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