Mad2 overexpression promotes aneuploidy and tumorigenesis in mice

Sotillo, R., Hernando, E., Díaz-Rodríguez, E., Teruya-Feldstein, J., Cordón-Cardo, C., Lowe, S. W., Benezra, R. (January 2007) Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell, 11 (1). pp. 9-23. ISSN 1535-6108

[thumbnail of Paper]
Preview
PDF (Paper)
Mad2.pdf

Download (2MB) | Preview
URL: https://www.ncbi.nlm.nih.gov/pubmed/17189715
DOI: 10.1016/j.ccr.2006.10.019

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: APC-DEPENDENT PROTEOLYSIS CHECKPOINT PROTEIN MAD2 MITOTIC CHECKPOINT GENE-EXPRESSION TRANSGENIC MICE CYCLIN-B CHROMOSOME MISSEGREGATION GENOMIC INSTABILITY ANAPHASE INITIATION SPINDLE CHECKPOINT
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Mad2
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: January 2007
Date Deposited: 02 Nov 2011 16:43
Last Modified: 10 Apr 2018 16:44
PMCID: PMC1850996
Related URLs:
URI: https://repository.cshl.edu/id/eprint/23143

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving