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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: Gogolin, Sina (VerfasserIn) , Batra, Richa (VerfasserIn) , Harder, Nathalie (VerfasserIn) , Ehemann, Volker (VerfasserIn) , Paffhausen, Tobias (VerfasserIn) , Diessl, Nicolle (VerfasserIn) , Sagulenko, Vitaliya (VerfasserIn) , Benner, Axel (VerfasserIn) , Gade, Stephan (VerfasserIn) , Nolte, Ingo (VerfasserIn) , Rohr, Karl (VerfasserIn) , König, Rainer (VerfasserIn) , Westermann, Frank (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2013
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
Volltext
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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 12.02.2020
First published: 24 November 2012
Beschreibung:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2012.11.028

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