Target gene therapy of glioma: overexpression of BAX gene under the control of both tissue-specific promoter and hypoxia-inducible element

Acta Biochim Biophys Sin (Shanghai). 2010 Apr;42(4):274-80. doi: 10.1093/abbs/gmq016.

Abstract

Glioma-specific transcription of tumor-killing genes has been exploited as a promising gene therapeutic modality in glioma patients. Musashi1 (Msi1) and GFAP gene promoters are both cancer-specific promoters. Optimized HIF-binding site (optHBS) sequence was newly found as efficient as EPO HREs used as enhancer in cancer gene therapy. We constructed 4optHBS-Msi1/GFAP promoters and tested their ability to mediate BAX expression to induce apoptosis in glioma cell lines. Our results demonstrated that 4optHBS-Msi1/GFAP promoters are apparently strong and glioma-selective promoters with potential application in targeted glioma gene therapy, and 4optHBS-Msi1/GFAPBAXa are valuable tools for glioma gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Binding Sites
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Flow Cytometry / methods
  • Genetic Therapy / methods*
  • Glial Fibrillary Acidic Protein / genetics
  • Glioma / therapy*
  • HeLa Cells
  • Humans
  • Hypoxia*
  • Hypoxia-Inducible Factor 1 / genetics
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • bcl-2-Associated X Protein / genetics*

Substances

  • BAX protein, human
  • Glial Fibrillary Acidic Protein
  • Hypoxia-Inducible Factor 1
  • bcl-2-Associated X Protein