| Online-Ressource |
Verfasst von: | Michaelis, Martin [VerfasserIn]  |
| Deimling, Andreas von [VerfasserIn]  |
Titel: | Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents |
Verf.angabe: | M. Michaelis, F. Rothweiler, B. Agha, S. Barth, Y. Voges, N. Löschmann, A. von Deimling, R. Breitling, H. Wilhelm Doerr, F. Rödel, D. Speidel, and J. Cinatl Jr |
E-Jahr: | 2012 |
Jahr: | 05 April 2012 |
Umfang: | 8 S. |
Fussnoten: | Gesehen am 29.11.2018 |
Titel Quelle: | Enthalten in: Cell death & disease |
Ort Quelle: | London [u.a.] : Nature Publishing Group, 2010 |
Jahr Quelle: | 2012 |
Band/Heft Quelle: | 3(2012), 4, Artikel-ID e294 |
ISSN Quelle: | 2041-4889 |
Abstract: | Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3rRITA10 μM to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells. |
DOI: | doi:10.1038/cddis.2012.35 |
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.
kostenfrei: Volltext ; Verlag: http://dx.doi.org/10.1038/cddis.2012.35 |
| kostenfrei: Volltext: https://www.nature.com/articles/cddis201235 |
| DOI: https://doi.org/10.1038/cddis.2012.35 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1584617020 |
Verknüpfungen: | → Zeitschrift |
Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents / Michaelis, Martin [VerfasserIn]; 05 April 2012 (Online-Ressource)