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 hypoxia is a common feature in these phenomena. We examined whether hypoxia influenced ETS-1 expression. Hypoxia induced ETS-1 in a human bladder cancer cell line, T24, and promoter analysis revealed that the deletion of -424 to -279 bp from the human ETS-1 promoter decreased the hypoxia-mediated inducibility. This region contained a hypoxia responsive element-like sequence, and HIF-1 bound to it under the hypoxic condition. Double-stranded synthetic oligonucleotides of this sequence as a decoy inhibited the hypoxia-mediated inducibility. These results indicate that hypoxia induces ETS-1 via the activity of HIF-1.
Oikawa
M
M
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Abe
M
M
Kurosawa
H
H
Hida
W
W
Shirato
K
K
Sato
Y
Y
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015687:Cell Hypoxia / Q000502:physiology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D008156:Luciferases