Cover Image

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Gogolin, Sina (Author) , Batra, Richa (Author) , Harder, Nathalie (Author) , Ehemann, Volker (Author) , Paffhausen, Tobias (Author) , Diessl, Nicolle (Author) , Sagulenko, Vitaliya (Author) , Benner, Axel (Author) , Gade, Stephan (Author) , Nolte, Ingo (Author) , Rohr, Karl (Author) , König, Rainer (Author) , Westermann, Frank (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Cancer letters
Year: 2012, Volume: 331, Issue: 1, Pages: 35-45
ISSN:1872-7980
DOI:10.1016/j.canlet.2012.11.028
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.canlet.2012.11.028
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383512006866
Get full text
Author Notes: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
Description
Summary: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.
Item Description:Gesehen am 12.02.2020
First published: 24 November 2012
Physical Description:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2012.11.028

Similar Items