Low rates of aneuploidy promote tumorigenesis while high rates of aneuploidy cause cell death and tumor suppression

摘要

An abnormal chromosome number, a condition known as aneuploidy, is a common characteristic of tumor cells. Because of this correlation, Boveri proposed aneuploidy to be a cause of tumorigenesis 100 years ago . However, this hypothesis remained untested due to the difficulty of selectively generating aneuploidy in the absence of other defects, particularly DNA damage. We determined that cells and mice with reduced levels of the mitosis-specific, centromere-linked motor protein CENP-E develop aneuploidy and chromosomal instability in vitro and in vivo in the absence of other defects, including DNA damage. CENP-E reduction causes aneuploidy and chromosomal instability due to the missegregation of one (or a few) whole chromosomes per division .