Abstract

Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigated whether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy. Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy.

Keywords

AneuploidyBreast cancerBiologyMitosisCancerCancer cellChromosome instabilityCancer researchApoptosisGenome instabilityDNA damageGeneticsGeneDNAChromosome

MeSH Terms

AneuploidyAnimalsApoptosisBreast NeoplasmsCell Cycle ProteinsFemaleHumansMiceMiceNudeMitosisNeoplasm TransplantationProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRNA InterferenceTumor CellsCultured

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Publication Info

Year
2011
Type
article
Volume
108
Issue
13
Pages
5384-5389
Citations
154
Access
Closed

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Cite This

Jewel A Daniel, Jonathan B. Coulter, Ju-Hyung Woo et al. (2011). High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells. Proceedings of the National Academy of Sciences , 108 (13) , 5384-5389. https://doi.org/10.1073/pnas.1007645108

Identifiers

DOI
10.1073/pnas.1007645108
PMID
21402910
PMCID
PMC3069188

Data Quality

Data completeness: 86%