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. 1998 Aug 18;95(17):10188–10193. doi: 10.1073/pnas.95.17.10188

Figure 4.

Figure 4

HRE and HIF-1 involvement in IGFBP-1 response to hypoxia. (A) Induction of reporter gene activity in HepG2 cells by hypoxia (expressed as fold increase above control, see text). Shown are the mean ± SD for four different experiments for IGFBP-1 HRE constructs and three different experiments with VEGF HRE constructs. Two-way analysis of variance revealed significantly increased reporter gene activity with a single copy of the IGFBP-1 HRE in the construct (P = 0.02) and with two copies of it (P = 0.0001). In normoxia, two copies of the IGFBP-1 HRE construct did not result in an increase in luciferase activity. hre, hypoxia response element; mut, mutant. (B) Transient transfection studies with the HRE in intron 1 of the IGFBP-1 gene attached to a luciferase reporter gene in a reporter construct cotransfected with a constitutively expressing HIF-1α plasmid (+HIF-1) or without (−HIF-1). Fold increase in luciferase activity is shown. VEGF served as a control (see text). Results show the mean ± SD of three different experiments. Two-way ANOVA revealed significantly increased reporter gene activity with cotransfection with the HIF-1α plasmid compared with controls (P = 0.001) and with two copies (P = 0.0001).