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Hypoxia Induces Transcription Factor ETS-1 via the Activity of Hypoxia-Inducible Factor-1

https://doi.org/10.1006/bbrc.2001.5927Get rights and content

Abstract

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 induciblity. These results indicate that hypoxia induces ETS-1 via the activity of HIF-1.

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    Citation Excerpt :

    Functional HREs with the same sequence are present in mammalian genes including toll-like receptors (2 and 6) (Kuhlicke et al., 2007), lipin 1 (Mylonis et al., 2012) and choline kinase α (Bansal et al., 2012). Moreover, the 5′ flanking sequence contains other predicted binding elements for factors that in non-crustacean animals participate in HIF signaling, including motifs for Sp1 (Higashimura et al., 2011), NF-κΒ (Taylor, 2008), HSF-1 (Baird et al., 2006), HSF-2 (Chen et al., 2011), MTF-1 (Murphy, 2004), AP-2 (Niebler et al., 2015), CRE-BP1 (ATF-2) (Choi et al., 2009), Ets (Oikawa et al., 2001), and C/EBPα (Yang et al., 2008). These factors may act together or independently from HIF-1; for example, NF-κΒ controls HIF-1α expression and additionally regulates inflammatory and apoptotic pathways during hypoxia (Taylor, 2008).

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