| |  Online-Ressource |
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| Verfasst von: | Höfflin, Rouven [VerfasserIn]  |
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| | Harlander, Sabine [VerfasserIn] |
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| | Schäfer, Silvia [VerfasserIn] |
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| | Metzger, Patrick [VerfasserIn] |
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| | Kuo, Fengshen [VerfasserIn] |
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| | Schönenberger, Désirée [VerfasserIn] |
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| | Adlesic, Mojca [VerfasserIn] |
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| | Peighambari, Asin [VerfasserIn] |
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| | Seidel, Philipp [VerfasserIn] |
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| | Chen, Chia-yi [VerfasserIn] |
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| | Consenza-Contreras, Miguel [VerfasserIn] |
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| | Jud, Andreas [VerfasserIn] |
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| | Lahrmann, Bernd [VerfasserIn] |
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| | Grabe, Niels [VerfasserIn] |
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| | Heide, Danijela [VerfasserIn] |
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| | Uhl, Franziska M. [VerfasserIn] |
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| | Chan, Timothy A. [VerfasserIn] |
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| | Duyster, Justus [VerfasserIn] |
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| | Zeiser, Robert [VerfasserIn] |
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| | Schell, Christoph [VerfasserIn] |
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| | Heikenwälder, Mathias [VerfasserIn] |
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| | Schilling, Oliver [VerfasserIn] |
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| | Hakimi, A. Ari [VerfasserIn] |
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| | Börries, Melanie [VerfasserIn] |
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| | Frew, Ian J. [VerfasserIn] |
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| Titel: | HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice |
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| Verf.angabe: | Rouven Hoefflin, Sabine Harlander, Silvia Schäfer, Patrick Metzger, Fengshen Kuo, Désirée Schönenberger, Mojca Adlesic, Asin Peighambari, Philipp Seidel, Chia-yi Chen, Miguel Consenza-Contreras, Andreas Jud, Bernd Lahrmann, Niels Grabe, Danijela Heide, Franziska M. Uhl, Timothy A. Chan, Justus Duyster, Robert Zeiser, Christoph Schell, Mathias Heikenwalder, Oliver Schilling, A. Ari Hakimi, Melanie Boerries & Ian J. Frew |
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| E-Jahr: | 2020 |
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| Jahr: | 17 August 2020 |
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| Umfang: | 21 S. |
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| Fussnoten: | Gesehen am 22.10.2020 |
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| Titel Quelle: | Enthalten in: Nature Communications |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2010 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 11(2020) Artikel-Nummer 4111, 21 Seiten |
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| ISSN Quelle: | 2041-1723 |
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| Abstract: | Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Herein we show using an autochthonous ccRCC model that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are required for the clear cell phenotype. Transcriptomic and proteomic analyses reveal that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2α-deficient tumours are characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlate with altered immune microenvironments in human ccRCC. These studies reveal an oncogenic role of HIF-1α in ccRCC initiation and suggest that alterations in the balance of HIF-1α and HIF-2α activities can affect different aspects of ccRCC biology and disease aggressiveness. |
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| DOI: | doi:10.1038/s41467-020-17873-3 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1038/s41467-020-17873-3 |
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| | Volltext: https://www.nature.com/articles/s41467-020-17873-3 |
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| | DOI: https://doi.org/10.1038/s41467-020-17873-3 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1736251171 |
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| Verknüpfungen: | → Zeitschrift |
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HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice / Höfflin, Rouven [VerfasserIn]; 17 August 2020 (Online-Ressource)
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