Document Detail

Spindle assembly checkpoint and p53 deficiencies cooperate for tumorigenesis in mice.
MedLine Citation:
PMID:  19065665     Owner:  NLM     Status:  MEDLINE    
The spindle assembly checkpoint (SAC) guards against chromosomal missegregation during mitosis. To investigate the role of SAC in tumor development, mice heterozygously knocked out for the mitotic arrest deficient (Mad) genes Mad1 and/or Mad2 were mated with p53(+/) (-) mice. Increased tumor frequencies were reproducibly observed in Mad2(+/) (-)p53(+/) (-) (88.2%) and Mad1(+/) (-)Mad2(+/) (-)p53(+/) (-) (95.0%) mice compared with p53(+/) (-) (66.7%) mice. Moreover, 53% of Mad2(+/) (-)p53(+/) (-) mice developed lymphomas compared with 11% of p53(+/) (-) mice. By examining chromosome content, increased loss in diploidy was seen in cells from Mad2(+/) (-)p53(+/) (-) versus p53(+/) (-) mice, correlating loss of SAC function, in a p53(+/) (-) context, with increased aneuploidy and tumorigenesis. The findings here provide evidence for a cooperative role of Mad1/Mad2 and p53 genes in preventing tumor development.
Ya-Hui Chi; Jerrold M Ward; Lily I Cheng; Junichiro Yasunaga; Kuan-Teh Jeang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  124     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-01-19     Completed Date:  2009-02-23     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1483-9     Citation Subset:  IM    
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Cell Cycle Proteins / genetics*
Crosses, Genetic
G1 Phase / genetics
Gene Frequency
Litter Size
Mice, Knockout
Mitotic Spindle Apparatus / pathology*
Mutation, Missense
Neoplasms / genetics*,  pathology
Protein-Serine-Threonine Kinases / deficiency*,  genetics
S Phase / genetics
Tumor Suppressor Protein p53 / deficiency*,  genetics
Grant Support
Z01 AI001023-01/AI/NIAID NIH HHS
Reg. No./Substance:
0/Cell Cycle Proteins; 0/MAD2 protein, mouse; 0/Tumor Suppressor Protein p53; EC spindle checkpoint protein; EC Kinases

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