Induction of genomic instability and activation of autophagy in artificial human aneuploid cells

Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Yohei Fujishima, Mitsuo Oshimura, Mitsuaki A. Yoshida

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Chromosome missegregation can lead to a change in chromosome number known as aneuploidy. Although aneuploidy is a known hallmark of cancer cells, the various mechanisms by which altered gene and/or DNA copy number facilitate tumorigenesis remain unclear. To understand the effect of aneuploidy occurring in non-tumorigenic human breast epithelial cells, we generated clones harboring artificial aneuploidy using microcell-mediated chromosome transfer. Our results demonstrate that clones with artificial aneuploidy of chromosome 8 or chromosome 22 both show inhibited proliferation and genomic instability. Also, the increased autophagy was observed in the artificially aneuploidy clones, and inhibition of autophagy resulted in increased genomic instability and DNA damage. In addition, the intracellular levels of reactive oxygen species were up-regulated in the artificially aneuploid clones, and inhibition of autophagy further increased the production of reactive oxygen species. Together, these results suggest that even a single extraneous chromosome can induce genomic instability, and that autophagy triggered by aneuploidy-induced stress is a mechanism to protect cells bearing abnormal chromosome number.

Original languageEnglish
Pages (from-to)19-30
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume790
DOIs
Publication statusPublished - 2016 Aug 1
Externally publishedYes

Keywords

  • Aneuploidy
  • Autophagy
  • Genomic instability
  • ROS
  • Trisomy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'Induction of genomic instability and activation of autophagy in artificial human aneuploid cells'. Together they form a unique fingerprint.

Cite this