Chromosome mis-segregation and cytokinesis failure in trisomic human cells

Elife. 2015 May 5;4:e05068. doi: 10.7554/eLife.05068.

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.

Keywords: CIN; aneuploidy; cancer; cell biology; chromosome; chromosomes; cytokinesis; genes; human; mis-segregation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amniotic Fluid / cytology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromosomal Instability*
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / metabolism
  • Chromosome Disorders / pathology
  • Chromosome Segregation
  • Chromosomes, Human, Pair 13 / chemistry*
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 13 / metabolism
  • Chromosomes, Human, Pair 7 / chemistry*
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 7 / metabolism
  • Colon / metabolism
  • Colon / pathology
  • Cytokinesis / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fetus
  • Gene Expression Regulation
  • Humans
  • Karyotyping
  • Phenotype
  • Pregnancy
  • Primary Cell Culture
  • Proteins / genetics*
  • Proteins / metabolism
  • Trisomy / genetics*
  • Trisomy / pathology
  • Trisomy 13 Syndrome

Substances

  • Cell Cycle Proteins
  • Proteins
  • SPART protein, human

Supplementary concepts

  • Chromosome 7, trisomy 7p

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.