MYCN-mediated overexpression of mitotic spindle regulatory genes and loss of p53-p21 function jointly support the survival of tetraploid neuroblastoma cells
High-risk neuroblastomas often harbor structural chromosomal alterations, including amplified MYCN, and usually have a near-di/tetraploid DNA index, but the mechanisms creating tetraploidy remain unclear. Gene-expression analyses revealed that certain MYCN/MYC and p53/pRB-E2F target genes, especiall...
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| Hauptverfasser: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2013
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| In: |
Cancer letters
Year: 2012, Jahrgang: 331, Heft: 1, Pages: 35-45 |
| ISSN: | 1872-7980 |
| DOI: | 10.1016/j.canlet.2012.11.028 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.canlet.2012.11.028 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383512006866 
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| Verfasserangaben: | Sina Gogolin, Richa Batra, Nathalie Harder, Volker Ehemann, Tobias Paffhausen, Nicolle Diessl, Vitaliya Sagulenko, Axel Benner, Stephan Gade, Ingo Nolte, Karl Rohr, Rainer König, Frank Westermann |
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| 245 | 1 | 0 | |a MYCN-mediated overexpression of mitotic spindle regulatory genes and loss of p53-p21 function jointly support the survival of tetraploid neuroblastoma cells |c Sina Gogolin, Richa Batra, Nathalie Harder, Volker Ehemann, Tobias Paffhausen, Nicolle Diessl, Vitaliya Sagulenko, Axel Benner, Stephan Gade, Ingo Nolte, Karl Rohr, Rainer König, Frank Westermann |
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| 520 | |a High-risk neuroblastomas often harbor structural chromosomal alterations, including amplified MYCN, and usually have a near-di/tetraploid DNA index, but the mechanisms creating tetraploidy remain unclear. Gene-expression analyses revealed that certain MYCN/MYC and p53/pRB-E2F target genes, especially regulating mitotic processes, are strongly expressed in near-di/tetraploid neuroblastomas. Using a functional RNAi screening approach and live-cell imaging, we identified a group of genes, including MAD2L1, which after knockdown induced mitotic-linked cell death in MYCN-amplified and TP53-mutated neuroblastoma cells. We found that MYCN/MYC-mediated overactivation of the metaphase-anaphase checkpoint synergizes with loss of p53-p21 function to prevent arrest or apoptosis of tetraploid neuroblastoma cells. | ||
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| 650 | 4 | |a Aneuploidy specific lethality genes | |
| 650 | 4 | |a Genomic instability | |
| 650 | 4 | |a Mitotic catastrophe | |
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| 650 | 4 | |a pRB | |
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