Hypoxia-specific downregulation of endogenous human VEGF-A gene by hypoxia-driven expression of artificial transcription factor

Tomoaki Mori, Jun Sasaki, Yasuhiro Aoyama, Takashi Sera

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Repression of vascular endothelial growth factor A (VEGF-A) is an attractive approach to cancer therapy. Although zinc-finger-based artificial transcription factors (ATFs) were constructed for human VEGF-A and constitutive expressions of ATFs were previously shown to downregulate the endogenous VEGF-A gene expression, repression of VEGF-A specifically in hypoxic tumors is desirable for therapeutic application of ATF technology. Here, we describe hypoxia-driven expression of the ATF for hypoxia-specific repression of human VEGF-A gene. We constructed a hypoxia-driven promoter for the ATF expression and placed it upstream of the ATF-encoding region. The resulting hypoxia-driven expression plasmids induced the expression of ATFs specifically in hypoxia, and the hypoxia-specific expression of ATFs effectively downregulated the VEGF-A expression in hypoxia, but not in normoxia. Thus, the engineered expression system of ATFs may enable repression of VEGF-A expression specifically in hypoxic tumors without affecting normal, healthy tissues.

Original languageEnglish
Pages (from-to)134-139
Number of pages6
JournalMolecular Biotechnology
Volume46
Issue number2
DOIs
Publication statusPublished - Oct 1 2010
Externally publishedYes

Keywords

  • Artificial transcription factor
  • Cancer
  • Hypoxia
  • Hypoxia-response element
  • Vascular endothelial growth factor A
  • Zinc-finger protein

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology

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