The combination of hypoxia-response enhancers and an oxygen-dependent proteolytic motif enables real-time imaging of absolute HIF-1 activity in tumor xenografts

Biochem Biophys Res Commun. 2007 Sep 7;360(4):791-6. doi: 10.1016/j.bbrc.2007.06.149. Epub 2007 Jul 5.


The transcriptional activity of hypoxia-inducible factor-1 (HIF-1) is associated with tumor malignancies; therefore, it is important to comprehend its dynamism in solid tumors. However, a molecular imaging strategy to accurately access it remains to be developed. We constructed here a novel HIF-1-dependent reporter gene, 5HREp-ODD-luc, in which 5 copies of the hypoxia-response element (5HRE) enhance expression of the oxygen-dependent degradation (ODD) domain and luciferase (luc) fusion under hypoxia. Because the ODD domain caused the oxygen-dependent degradation of the ODD-Luc protein, the novel reporter gene showed little leak of luminescence under normoxia. Such a property caused an increase of the hypoxia-responsiveness up to about 4.7 x 10(4) -fold. Moreover, the ODD domain caused rapid degradation of the ODD-Luc protein under normoxia, the luminescence reflected the dynamism of HIF-1 activity in real-time. The superiority of the novel reporter gene will surely accelerate analysis of the intratumoral HIF-1 activity during tumor progression and cancer treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Hypoxia / drug effects*
  • DNA Primers
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Hydrolysis
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neoplasms / metabolism*
  • Oxygen / metabolism*
  • Transplantation, Heterologous


  • DNA Primers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen