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eLifeVolume 4, Issue MAY, 5 May 2015, Article number e05068, 23p

Chromosome mis-segregation and cytokinesis failure in trisomic human cells(Article)(Open Access)

  • Nicholson, J.M.,
  • Macedo, J.C.,
  • Mattingly, A.J.,
  • Wangsa, D.,
  • Camps, J.,
  • Lima, V.,
  • Gomes, A.M.,
  • Dória, S.,
  • Ried, T.,
  • Logarinho, E.,
  • Cimini, D.
  • View Correspondence (jump link)
  • aDepartment of Biological Sciences, Virginia Tech, Blacksburg, United States
  • bVirginia Bioinformatics Institute, Virginia Tech, Blacksburg, United States
  • cAging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
  • dInstituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Porto, Portugal
  • eCell Division Unit, Department of Experimental Biology, Universidade do Porto, Porto, Portugal
  • fGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States
  • gDepartment of Genetics, Universidade do Porto, Porto, Portugal
  • hCell and Tissue Biology, School of Dentistry, University of California, San Francisco, San Francisco, United States
  • iGastrointestinal and Pancreatic Oncology Group, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut D’Investigacions Biome` diques August Pi i Sunyer, Barcelona, Spain

Abstract

Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome. © 2015, eLife Sciences Publications Ltd. All rights reserved.

Indexed keywords

EMTREE drug terms:peptides and proteinsspastinproteinSPG20 protein, human
EMTREE medical terms:aneuploidyArticlechromosome 13chromosome 7chromosome segregationcolorectal cancerconfocal microscopycontrolled studycopy number variationcytokinesisfluorescence imagingfluorescence in situ hybridizationgene expressionhumanhuman cellimmunohistochemistrymetaphasephenotypeprotein localizationtime-lapse video microscopytrisomyupregulationWestern blottingamnion fluidchemistrychromosomal instabilitychromosome disorderchromosome segregationcoloncytokinesiscytologyepithelium cellfemalefetusgene expression regulationgeneticskaryotypingmetabolismpathologypregnancyprimary cell culturetrisomytumor cell line
MeSH:Amniotic FluidCell Line, TumorChromosomal InstabilityChromosome DisordersChromosome SegregationChromosomes, Human, Pair 13Chromosomes, Human, Pair 7ColonCytokinesisEpithelial CellsFemaleFetusGene Expression RegulationHumansKaryotypingPhenotypePregnancyPrimary Cell CultureProteinsTrisomy

Chemicals and CAS Registry Numbers:

spastin, 252912-06-4; protein, 67254-75-5;

Proteins; SPG20 protein, human

Funding details

Funding sponsor Funding number Acronym
National Institutes of Health
See opportunities by NIH		ZIABC010833NIH
National Institutes of Health
See opportunities by NIH		ZIABC010835NIH
  • ISSN: 2050084X
  • Source Type: Journal
  • Original language: English
  • DOI: 10.7554/eLife.05068
  • PubMed ID: 25942454
  • Document Type: Article
  • Publisher: eLife Sciences Publications Ltd

  Cimini, D.; Department of Biological Sciences, Virginia Tech, Blacksburg, United States
© Copyright 2017 Elsevier B.V., All rights reserved.

Cited by 40 documents

Barroso-Vilares, M. , Logarinho, E.
Chromosomal instability and pro-inflammatory response in aging
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Wangsa, D. , Braun, R. , Stuelten, C.H.
Induced Chromosomal Aneuploidy Results in Global and Consistent Deregulation of the Transcriptome of Cancer Cells
(2019) Neoplasia (United States)
Tijhuis, A.E. , Johnson, S.C. , McClelland, S.E.
The emerging links between chromosomal instability (CIN), metastasis, inflammation and tumour immunity
(2019) Molecular Cytogenetics
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