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- W4362490717 abstract "<div>Abstract<p>The hypoxia-inducible transcription factors (HIF) 1α and HIF-2α play a critical role in cellular response to hypoxia. Elevated HIF-α expression correlates with poor patient survival in a large number of cancers. Recent evidence suggests that HIF-2α appears to be preferentially expressed in neuronal tumor cells that exhibit cancer stem cell characteristics. These observations suggest that expression of HIF-1α and HIF-2α is differentially regulated in the hypoxic tumor microenvironment. However, the underlying mechanisms remain to be fully investigated. In this study, we investigated the transcriptional regulation of <i>HIF</i>-<i>1α</i> and <i>HIF</i>-<i>2α</i> under different physiologically relevant hypoxic conditions. We found that transcription of <i>HIF</i>-<i>2α</i> was consistently increased by hypoxia, whereas transcription of <i>HIF</i>-<i>1α</i> showed variable levels of repression. Mechanistically, differential regulation of <i>HIF</i>-<i>α</i> transcription involved hypoxia-induced changes in acetylation of core histones H3 and H4 associated with the proximal promoters of the <i>HIF</i>-<i>1α</i> or <i>HIF</i>-<i>2α</i> gene. We also found that, although highly stable under acute hypoxia, HIF-1α and HIF-2α proteins become destabilized under chronic hypoxia. Our results have thus provided new mechanistic insights into the differential regulation of <i>HIF</i>-<i>1α</i> and <i>HIF</i>-<i>2α</i> by the hypoxic tumor microenvironment. These findings also suggest an important role of HIF-2α in the regulation of tumor progression under chronic hypoxia. <i>Mol Cancer Res; 9(6); 757–65. ©2011 AACR</i>.</p></div>" @default.
- W4362490717 created "2023-04-05" @default.
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- W4362490717 date "2023-04-03" @default.
- W4362490717 modified "2023-10-14" @default.
- W4362490717 title "Data from Differential Hypoxic Regulation of Hypoxia-Inducible Factors 1α and 2α" @default.
- W4362490717 doi "https://doi.org/10.1158/1541-7786.c.6542202.v1" @default.
- W4362490717 hasPublicationYear "2023" @default.
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