TY - JOUR
T1 - Aneuploidy Acts Both Oncogenically and as a Tumor Suppressor
AU - Weaver, Beth A.A.
AU - Silk, Alain D.
AU - Montagna, Cristina
AU - Verdier-Pinard, Pascal
AU - Cleveland, Don W.
N1 - Funding Information:
The authors would like to thank Dr. Nissi Varki and the UCSD histology core, Janet Folmer (Johns Hopkins), and Dr. Dwayne Breining from the Department of Pathology (AECOM, Bronx, NY) for preparation and analysis of histological specimens. We would also like to thank Dr. James Feramisco and the UCSD Cancer Center microscopy facility. This work was supported by a National Institutes of Health grant to D.W.C. (GM29513). B.A.A.W. was supported, in part, by a postdoctoral fellowship from Philip Morris USA Inc. and Philip Morris international. Salary support for D.W.C. was provided by the Ludwig Institute for Cancer Research.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - CELLCYCLE
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U2 - 10.1016/j.ccr.2006.12.003
DO - 10.1016/j.ccr.2006.12.003
M3 - Article
C2 - 17189716
AN - SCOPUS:33846065784
SN - 1535-6108
VL - 11
SP - 25
EP - 36
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -
