BRG1 expression is increased in human glioma and controls glioma cell proliferation, migration and invasion in vitro

J Cancer Res Clin Oncol. 2012 Jun;138(6):991-8. doi: 10.1007/s00432-012-1172-8. Epub 2012 Feb 24.

Abstract

Purpose: The purposes of our study were to elucidate the role of BRG1 in the development of human glioma and to determine the effect of BRG1 on glioma cell growth, migration and invasion.

Methods: Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 190 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues. We studied glioma cell proliferative ability with reduced BRG1 expression by siRNA using CCK-8 cell proliferation assay and cell cycle analysis. We studied the role of BRG1 in glioma cell migration and invasion by cell migration assay and matrigel invasion assay. We performed western blot to detect cyclin D1, cyclin B1 and MMP-2 protein expression. We also detected MMP-2 enzyme activity by gelatin zymography.

Results: Our results showed that BRG1 expression was increased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 for both). We did not find any correlation between BRG1 expression and clinicopathological parameters. In addition, we found that knockdown of BRG1 in glioma cell lines inhibits cell growth due to the G1 phase arrest by downregulating cyclin D1. We further demonstrated that silencing of BRG1 in glioma cells inhibited the cell migration and invasion abilities, and downregulation of MMP-2 expression greatly contributed to the reduced cell invasion and migration abilities.

Conclusions: Our data indicated that BRG1 expression is significantly increased in human glioma and it may be involved in the process of glioma cell proliferation, migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Cycle / genetics
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • DNA Helicases / biosynthesis*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Knockdown Techniques / methods
  • Gene Silencing
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA, Small Interfering / genetics
  • Sincalide / genetics
  • Sincalide / metabolism
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CCNB1 protein, human
  • CCND1 protein, human
  • Cyclin B1
  • Nuclear Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Cyclin D1
  • Matrix Metalloproteinase 2
  • SMARCA4 protein, human
  • DNA Helicases
  • Sincalide