Ets-1 upregulates HER2-induced MMP-1 expression in breast cancer cells

Biochem Biophys Res Commun. 2008 Dec 12;377(2):389-394. doi: 10.1016/j.bbrc.2008.09.135. Epub 2008 Oct 11.

Abstract

The human epidermal growth factor receptor-2 (HER2) plays an important role in breast cancer. Enhanced Ets-1 activity has recently been shown to be associated with breast cancer pathogenesis. To test the role of Ets-1 in breast cancer cells in relation to the expression of HER2 and MMP-1, we transiently overexpressed Ets-1 and/or HER2 in MCF-7 breast cancer cells and comprehensively searched for genes related to HER2 and Ets-1 using cDNA microarray analysis. The expression of matrix metalloproteinase (MMP) genes was enhanced by the overexpression of HER2/Ets-1. We analyzed the relationship between HER2-induced MMP-1 expression and the transcription factor Ets-1, which has significant activity in breast cancer pathogenesis. Our results demonstrate that HER2-induced MMP-1 expression is positively regulated by Ets-1 in breast cancer cells. This study confirms that Ets-1 is a downstream effector of oncogenic HER2, associated with MMP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Humans
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Transfection

Substances

  • ETS1 protein, human
  • Proto-Oncogene Protein c-ets-1
  • ErbB Receptors
  • Receptor, ErbB-2
  • Matrix Metalloproteinase 1