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Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1.

Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1. Research Abstract Details 

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  • Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1. Abstract Text:

    The hypoxia-inducible transcription factors (HIF)-1alpha and -2alpha mediate responses to hypoxia, such as tumor neovascularization. To determine the function of HIF-2alpha in vascular endothelial cells (ECs), we examined vascular formation in HIF-2alpha knockdown (kd/kd) mice transplanted with tumors. We observed that both the tumor size and the number of large vessels growing within transplanted melanomas were significantly reduced in kd/kd recipients compared with wild-type (WT) mice. In contrast, we observed a similar extent of vascular formation within fibrosarcomas transplanted from either kd/kd or WT mice into WT recipients. Thus, HIF-2alpha expression in host animal ECs, but not in the tumor cells, is crucial for tumor neovascularization. HIF-2alpha may function through ephrin A1 as the expression of ephrin A1 and related genes was markedly reduced in kd/kd ECs, and HIF-2alpha specifically bound a hypoxia-response element sequence in the ephrin A1 promoter. Treatment of WT ECs with an ephrin A1 inhibitor (ephrin A1-Fc) also impaired neovascularization. We conclude that in ECs, HIF-2alpha plays an essential role in vascular remodeling during tumor vascularization through activation of at least ephrin A1.

    Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1. Publishing Authors By Initials

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    Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 283

    Page Numbers: 18926-36

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 23

    MONTH: 04

    YEAR: 2008

    Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

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    Grant and Affiliation Information for Hypoxia-inducible Transcription Factor-2{alpha} in Endothelial Cells Regulates Tumor Neovascularization through Activation of Ephrin A1.

    AFFILIATION: Department of Regenerative Medicine, Department of Molecular and Developmental Biology, Center for Tsukuba Advanced Research Alliance, Japan Science and Technology-Exploratory Research for Advanced Technology Environmental Response Project.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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