Quantitative analysis of topoisomerase II alpha and evaluation of its effects on cell proliferation and apoptosis in glioblastoma cancer stem cells

Neurosci Lett. 2012 Jun 19;518(2):138-43. doi: 10.1016/j.neulet.2012.04.071. Epub 2012 May 6.

Abstract

DNA topoisomerase II alpha (Topo-IIα) is an essential nuclear enzyme with its up-regulation demonstrated in different tumors. This study is to evaluate the expression of Topo-IIα in glioblastoma cancer stem cells (CSCs) and its effects on cell proliferation and apoptosis. We observed the expression differences of Topo-IIα gene transcript in CSCs and non-CSCs in glioblastoma cell line U87 by quantitative real-time PCR and western blot; we silenced Topo-IIα expression in U87 CSCs using Topo-IIα-specific siRNA to investigate the role of Topo-IIα in cell proliferation, cell cycle, and apoptosis. We found higher expression of Topo-IIα in CSCs than in non-CSCs. After using Topo-IIα-specific siRNA to silence the expression of Topo-IIα gene, we observed decreasing cell proliferation, cell cycle arrest, and induction of apoptosis in CSCs, which suggest that Topo-IIα contributes to both cell proliferation and/or cell survival. Topo-IIα may be a novel marker of cell proliferation and/or survival factor in glioblastoma CSCs. It may be a potential target that will open up new opportunities to develop therapeutic strategies for gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Apoptosis*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • DNA Topoisomerases, Type II / analysis*
  • DNA Topoisomerases, Type II / biosynthesis
  • DNA Topoisomerases, Type II / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Flow Cytometry
  • Glioblastoma / enzymology*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / pathology
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Transfection

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RNA, Small Interfering
  • DNA Topoisomerases, Type II