Aneuploidy Acts Both Oncogenically and as a Tumor Suppressor

Abstract

An abnormal chromosome number, aneuploidy, is a common characteristic of tumor cells. Boveri proposed nearly 100 years ago that aneuploidy causes tumorigenesis, but this has remained untested due to the difficulty of selectively generating aneuploidy. Cells and mice with reduced levels of the mitosis-specific, centromere-linked motor protein CENP-E are now shown to develop aneuploidy and chromosomal instability in vitro and in vivo. An increased rate of aneuploidy does drive an elevated level of spontaneous lymphomas and lung tumors in aged animals. Remarkably, however, in examples of chemically or genetically induced tumor formation, an increased rate of aneuploidy is a more effective inhibitor than initiator of tumorigenesis. These findings reveal a role of aneuploidy and chromosomal instability in preventing tumorigenesis.

Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

“…It is also important to note that aneuploidy caused by mitotic error can act both oncogenically and as a tumor suppressor depending on the level of induced cell division mistakes as well as the genetic background of the cells. Typically low rates of aneuploidy are associated with tumorigenesis while high rates of aneuploidy cause cell death and tumor suppression (Weaver and Cleveland, 2008;Weaver et al, 2007).…”

Aging by epigenetics—A consequence of chromatin damage?

“…Recent studies in yeast showed that aneuploidy confers various altered cell phenotypes, including a proliferative impairment, which might contribute to decreased tissue renewal capacity with age [102]. Aneuploidy may also promote cancer [103], a disease for which age is the biggest risk factor.…”

HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint

“…In mammalian cells, APC/C is regulated by the mitotic checkpoint complex (MCC), which is composed of BubR1, Bub3, Mad2 and CDC20 (Sudakin et al, 2001). Mouse embryonic fibroblasts (MEFs) derived from heterozygous BubR1 þ /À , Mad2 þ /À or CENP-E þ /À mice exhibit chromosome missegregation and aneuploidy (Michel et al, 2001;Dai et al, 2004;Weaver et al, 2007).…”