Mad2 overexpression promotes aneuploidy and tumorigenesis in mice.
Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes.
Sotillo
Rocío
R
Cancer Biology and Genetics Program, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hernando
Eva
E
Díaz-Rodríguez
Elena
E
Teruya-Feldstein
Julie
J
Cordón-Cardo
Carlos
C
Lowe
Scott W
SW
Benezra
Robert
R
D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D043171:Chromosomal Instability; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D064246:Mad2 Proteins; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse