Visualization of Hypoxia-Inducible Factor-1 Transcriptional Activation in C6 Glioma Using Luciferase and Sodium Iodide Symporter Genes

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor of hy-poxic response in cancer cells and is associated with tumor pro-gression, angiogenesis, metastasis, and resistance to therapy. We assessed whether the human sodium iodide symporter (NIS) reporter systemscanbeused to visualize transcriptional ac-tivation of HIF-1 in C6 glioma. Methods: Two types of plasmid-expressing human NIS or luciferase (Luc) genes, controlled by 5 copies of hypoxia response element (5HRE), were constructed: p5HRE-NIS or p5HRE-Luc. C6 glioma cells were stably trans-fected with p5HRE-NIS or p5HRE-Luc plasmids (C6-5HRE-NIS or C6-5HRE-Luc). Hypoxic conditions were modeled by expos-ing culture medium to desferrioxamine (DFO) or a low oxygen at-mosphere (,1 % O2) in a hypoxic chamber. HIF-1 transcription activity was assessed bymeasuring cellular 125I uptake and lumi-nescent intensities. Reverse-transcription polymerase chain re