title: Induction of genomic instability and activation of autophagy in artificial human aneuploid cells.
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.
authors.affiliation: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ariyoshi
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Tomisato
authors.initials: T
authors.lastname: Miura
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Fujishima
authors.affiliation: Chromosome Engineering Research Center (CERC), Tottori University, Nishicho 86, Yonago, Tottori 683-8503, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.affiliation: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan. Electronic address: ariyoshi@hirosaki-u.ac.jp.
authors.forename: Mitsuaki A
authors.initials: MA
authors.lastname: Yoshida
mesh_terms: D000782:Aneuploidy; D000818:Animals; D058045:Artificial Cells / Q000378:metabolism*; D001343:Autophagy / Q000235:genetics*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D020223:Chromosome Painting; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Aneuploidy; Autophagy; Genomic instability; ROS; Trisomy