Upregulation of GRIM-19 inhibits the growth and invasion of human breast cancer cells

Mol Med Rep. 2015 Aug;12(2):2919-25. doi: 10.3892/mmr.2015.3757. Epub 2015 May 7.

Abstract

Gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19), a novel IFN-β/retinoic acid-inducible gene product, has been identified as a potential tumor suppressor, which is associated with the inhibition of tumor growth. GRIM-19 has been demonstrated to be downregulated in the ovarian tissue of patients with breast cancer, however, its role in breast cancer remains to be fully elucidated. In the present study, a recombinant eukaryotic expression plasmid carrying GRIM-19 was constructed and then transfected into the MCF7 human breast cancer cell line to examine its effects on breast cancer cell growth, migration and invasion using several in vitro approaches. The results demonstrated that upregulation GRIM-19 in the MCF7 cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell apoptosis. Additionally, upregulation of GRIM-19 also suppressed the secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF). It was also demonstrated that the activation of signal transducer and activator of transcription 3 (STAT3) was downregulated by the expression of GRIM-19. These results revealed that overexpression of the GRIM-19 gene may be an effective approach to control the growth and invasion of human breast cancer cells.

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • Plasmids / genetics
  • Plasmids / metabolism
  • Real-Time Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Up-Regulation
  • Urokinase-Type Plasminogen Activator / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • STAT3 Transcription Factor
  • Vascular Endothelial Growth Factor A
  • NADH, NADPH Oxidoreductases
  • NDUFA13 protein, human
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9