| |  Online-Ressource |
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| Verfasst von: | Kaczorowski, Adam [VerfasserIn]  |
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| | Tolstov, Yanis [VerfasserIn] |
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| | Falkenstein, Michael [VerfasserIn] |
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| | Vasioukhin, Valeri [VerfasserIn] |
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| | Prigge, Elena-Sophie [VerfasserIn] |
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| | Geisler, Christine [VerfasserIn] |
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| | Kippenberger, Maximilian [VerfasserIn] |
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| | Nientiedt, Cathleen [VerfasserIn] |
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| | Ratz, Leonie [VerfasserIn] |
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| | Kuryshev, Vladimir [VerfasserIn] |
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| | Herpel, Esther [VerfasserIn] |
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| | Kristiansen, Glen [VerfasserIn] |
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| | Sültmann, Holger [VerfasserIn] |
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| | Stenzinger, Albrecht [VerfasserIn] |
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| | Knebel Doeberitz, Magnus von [VerfasserIn] |
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| | Hohenfellner, Markus [VerfasserIn] |
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| | Duensing, Anette [VerfasserIn] |
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| | Duensing, Stefan [VerfasserIn] |
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| Titel: | Rearranged ERG confers robustness to prostate cancer cells by subverting the function of p53 |
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| Verf.angabe: | Adam Kaczorowski, Ph.D., Yanis Tolstov, Ph.D., Michael Falkensteina, Valeri Vasioukhin, Ph.D., Elena-Sophie Prigge, M.D., Christine Geislerd, Maximilian Kippenbergera, Cathleen Nientiedt, M.D., Leonie Ratz, M.D., Ph.D.,Vladimir Kuryshev, Ph.D., Esther Herpel, M.D., Glen Kristiansen, M.D.,Holger Sültmann, Ph.D., Albrecht Stenzinger, M.D., Magnus von Knebel Doeberitz, M.D., Markus Hohenfellner, M.D., Anette Duensing, M.D., Stefan Duensing, M.D. |
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| E-Jahr: | 2020 |
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| Jahr: | 13 July 2020 |
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| Umfang: | 10 S. |
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| Fussnoten: | Gesehen am 18.09.2020 |
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| Titel Quelle: | Enthalten in: Urologic oncology |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1995 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 38(2020), 9, Seite 736.e1-736.e10 |
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| ISSN Quelle: | 1873-2496 |
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| Abstract: | Objective - ERG rearrangements are frequent and early events in prostate cancer. The functional role of rearranged ERG, however, is still incompletely understood. ERG rearrangements are maintained during prostate cancer progression suggesting that they may confer a selective advantage. The molecular basis of this notion is the subject of this study. - Methods - A variety of immunological methods were used to characterize the effects of rearranged ERG on p53. Consequences of an overexpression of N-terminally deleted ERG on p53 function were interrogated by measuring apoptosis and cellular senescence in the presence or absence of exogenous DNA damage. Effects of N-terminally deleted ERG on the transactivation function of p53 were analyzed by qRT-PCR. - Results - We show that overexpression of ERG leads to an increased basal level of DNA damage and a stabilization of p53 that involves a sequestration of its E3 ubiquitin ligase, MDM2, into nucleoli. A higher p53 expression was also observed in vivo in an ERG-overexpressing prostatic intraepithelial neoplasia mouse model. The correlation between ERG and p53 expression was corroborated in 163 patients with prostate cancer. ERG overexpression was found to inhibit both apoptosis and cellular senescence induced by exogenous DNA damage. Mechanistically, this protective effect of ERG involved an abrogation of the DNA damage-induced expression of p53 target genes. - Conclusions - By protecting tumor cells from the antiproliferative consequences of genotoxic stress, ERG may allow the survival and proliferation of genomically unstable tumor cells. Targeting ERG may therefore represent a promising strategy to suppress such adverse features during prostate cancer progression. |
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| DOI: | doi:10.1016/j.urolonc.2020.06.016 |
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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: https://doi.org/10.1016/j.urolonc.2020.06.016 |
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| | Volltext: http://www.sciencedirect.com/science/article/pii/S1078143920302878 |
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| | DOI: https://doi.org/10.1016/j.urolonc.2020.06.016 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Apoptosis |
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| | DNA damage |
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| | ERG |
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| | p53 |
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| | Prostate cancer |
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| K10plus-PPN: | 1733314172 |
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| Verknüpfungen: | → Zeitschrift |
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Rearranged ERG confers robustness to prostate cancer cells by subverting the function of p53 / Kaczorowski, Adam [VerfasserIn]; 13 July 2020 (Online-Ressource)
