title: 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.
authors.affiliation: 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.
authors.forename: Beth A A
authors.initials: BA
authors.lastname: Weaver
authors.forename: Alain D
authors.initials: AD
authors.lastname: Silk
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.forename: Pascal
authors.initials: P
authors.lastname: Verdier-Pinard
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: 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*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E