Breast cancer invasion and progression by MMP-9 through Ets-1 transcription factor

Gene. 2019 Aug 30;711:143952. doi: 10.1016/j.gene.2019.143952. Epub 2019 Jun 29.

Abstract

Ets-1 is one of the crucial member of transcription factor family which share a unique DNA binding domain. It is predominantly expressed in various tumor subtypes and has shown its association in the regulation of various important genes which include ECM-degrading proteases. Our study aimed to understand the mechanism(s) in the pathogenesis of breast carcinogenesis by Ets-1 transcription factor and its downstream target gene MMP-9. Role of Ets-1 in MCF-7 and MDA-MB-231 breast cancer cells was studied by RNA-interference in combination with pull down and ChIP assays to identify the regulation of MMP-9 in these cell lines. Our results showed that transfection of Ets-1 siRNA in breast cancer cell lines resulted in downregulation of Ets-1 and MMP-9. Ets-1 knock down also showed reduced cell invasion and altered expression of EMT markers. Moreover, we could also predict that MMP-9 gene promoter harbors a binding site for Ets-1 transcription factor may be responsible in direct transactivation of Ets-1 along with EMT markers. Phenotypic changes and molecular alterations that may result in increased aggressiveness/invasiveness and metastatic nature of cancerous cells may lead to changes in EMT markers. Therefore, these findings may suggest a plausible role of Ets-1 dependent regulation of MMP-9 gene and may have a significant impact on breast carcinogenesis.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism*

Substances

  • ETS1 protein, human
  • Proto-Oncogene Protein c-ets-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9