Studying chromosome instability in the mouse.
Aneuploidy has long been recognized as one of the hallmarks of cancer. It nonetheless remains uncertain whether aneuploidy occurring early in the development of a cancer is a primary cause of oncogenic transformation, or whether it is an epiphenomenon that arises from a general breakdown in cell cycle control late in tumorigenesis. The accuracy of chromosome segregation is ensured both by the intrinsic mechanics of mitosis and by an error-checking spindle assembly checkpoint. Many cancers show altered expression of proteins involved in the spindle checkpoint or in proteins implicated in other mitotic processes. To understand the role of aneuploidy in the initiation and progression of cancer, a number of spindle checkpoint genes have been disrupted in mice, most through conventional gene targeting (to create germ-line knockouts). We describe the consequence of these mutations with respect to embryonic development, tumor progression and an unexpected link to premature aging; readers are referred elsewhere [1] for a discussion of other cell cycle regulators.
Foijer
Floris
F
Harvard Medical School, Department of Systems Biology, 200 Longwood Avenue, Boston, MA 02115, USA.
Draviam
Viji M
VM
Sorger
Peter K
PK
D000782:Aneuploidy; D000818:Animals; D001324:Autoantigens; D018797:Cell Cycle Proteins / Q000502:physiology; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000172:deficiency; D018385:Centrosome / Q000502:physiology; D043171:Chromosomal Instability / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency; D020090:Chromosome Segregation / Q000502:physiology; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D064246:Mad2 Proteins; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D023421:Models, Animal; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology; D008941:Spindle Apparatus
D001324:Autoantigens; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D064246:Mad2 Proteins; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins