Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1

ETS-1 plays an important role in angiogenesis and cancer invasion, and hypo xia is a common feature in these phenomena. We examined whether hypoxia inf luenced ETS-1 expression. Hypoxia induced ETS-1 in a human bladder cancer c ell line, T24, and promoter analysis revealed that the deletion of -424 to -279 bp from the human ETS-1 promoter decreased the hypoxia-mediated induci bility. This region contained a hypoxia responsive element-like sequence, a nd HIF-1 bound to it under the hypoxic condition. Double-stranded synthetic oligonucleotides of this sequence as a decoy inhibited the hypoxia-mediate d induciblity. These results indicate that hypoxia induces ETS-1 via the ac tivity of HIF-1. (C) 2001 Academic Press.