Aneuploidy acts both oncogenically and as a tumor suppressor.
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.
Weaver
Beth A A
BA
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Silk
Alain D
AD
Montagna
Cristina
C
Verdier-Pinard
Pascal
P
Cleveland
Don W
DW
D000367:Age Factors; D000782:Aneuploidy; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009369:Neoplasms / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E