The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis

Nat Med. 2000 Feb;6(2):189-95. doi: 10.1038/72294.

Abstract

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Cell Division / physiology
  • Cell Transformation, Neoplastic*
  • DNA Primers
  • Female
  • Gene Expression Regulation / physiology*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / pathology
  • Promoter Regions, Genetic
  • Protein Binding
  • Receptor, ErbB-2 / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • DNA Primers
  • Transcription Factors
  • transcription factor PEA3
  • Receptor, ErbB-2