MYCN-mediated overexpression of mitotic spindle regulatory genes and loss of p53-p21 function jointly support the survival of tetraploid neuroblastoma cells.
Cancer Lett
; 331(1): 35-45, 2013 Apr 30.
Article
en En
| MEDLINE
| ID: mdl-23186832
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ploidias
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Proteínas Nucleares
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Proteína p53 Supresora de Tumor
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Apoptosis
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Proteínas Oncogénicas
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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Huso Acromático
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Neuroblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
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Infant
Idioma:
En
Año:
2013
Tipo del documento:
Article