Document Detail


Tpx2 controls spindle integrity, genome stability, and tumor development.
MedLine Citation:
PMID:  22266221     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tpx2 is a microtubule-associated protein that activates the cell-cycle kinase Aurora A and regulates the mitotic spindle. Overexpression of Tpx2 is associated with the development of different human tumors and strongly correlates with chromosomal instability. By analyzing a conditional null mutation in the mouse Tpx2 gene, we show here that Tpx2 expression is essential for spindle function and chromosome segregation in the mouse embryo. Conditional genetic ablation of Tpx2 in primary cultures resulted in deficient microtubule nucleation from DNA and aberrant spindles during prometaphase. These cells eventually exited from mitosis without chromosome segregation. In addition, Tpx2 haploinsufficiency led to the accumulation of aneuploidies in vivo and increased susceptibility to spontaneous lymphomas and lung tumors. Together, our findings indicate that Tpx2 is essential for maintaining genomic stability through its role in spindle regulation. Subtle changes in Tpx2 expression may favor tumor development in vivo.
Authors:
Cristina Aguirre-Portolés; Alexander W Bird; Anthony Hyman; Marta Cañamero; Ignacio Pérez de Castro; Marcos Malumbres
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-20
Journal Detail:
Title:  Cancer research     Volume:  72     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-16     Completed Date:  2012-05-14     Revised Date:  2014-06-12    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1518-28     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoma / genetics
Animals
Cell Cycle Proteins / genetics,  metabolism*
Cell Transformation, Neoplastic / genetics*
Cells, Cultured
Chromosome Segregation / genetics
Female
Genomic Instability*
Haploinsufficiency
Lung Neoplasms / genetics
Lymphoma / genetics
Mice
Microtubule-Associated Proteins / genetics,  metabolism*
Nuclear Proteins / genetics,  metabolism*
Spindle Apparatus / metabolism*
Grant Support
ID/Acronym/Agency:
08-0188//Worldwide Cancer Research
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Microtubule-Associated Proteins; 0/Nuclear Proteins; 0/TPX2 protein, mouse

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