Mouse Tumor Biology Database (MTB)
MTB Home   Help
Search for Help
 
in these sections
Search Forms
Tumor
Strain
Genetics
Pathology Images
Reference
Advanced
Search MTB Using Human Genes
Gene Expression Data Sets

Additional Resources
new PDX Like Me
PDX Finder
PDX Model Search
Faceted Tumor Search
Dynamic Tumor Frequency Grid
Other Cancer Websites
Immunohistochemistry
Lymphoma Pathology

Mouse Genome Informatics
The Jackson Laboratory
Citing These Resources
Warranty Disclaimer
& Copyright Notice

Send Questions and
Comments to User Support.

Last Database Update
2020-07-12
MTB 3.0
 
HelpHelp and Documentation Reference Detail  
Reference
Title: Overexpression of Eg5 causes genomic instability and tumor formation in mice.
Authors: Castillo A; Morse HC 3rd; Godfrey VL; Naeem R; Justice MJ
Journal: Cancer Res
Volume: 67
Issue: 21
Year: 2007
Pages: 10138-47
Abstract: Proper chromosome segregation in eukaryotes is driven by a complex superstructure called the mitotic spindle. Assembly, maintenance, and function of the spindle depend on centrosome migration, organization of microtubule arrays, and force generation by microtubule motors. Spindle pole migration and elongation are controlled by the unique balance of forces generated by antagonistic molecular motors that act upon microtubules of the mitotic spindle. Defects in components of this complex structure have been shown to lead to chromosome missegregation and genomic instability. Here, we show that overexpression of Eg5, a member of the Bim-C class of kinesin-related proteins, leads to disruption of normal spindle development, as we observe both monopolar and multipolar spindles in Eg5 transgenic mice. Our findings show that perturbation of the mitotic spindle leads to chromosomal missegregation and the accumulation of tetraploid cells. Aging of these mice revealed a higher incidence of tumor formation with a mixed array of tumor types appearing in mice ages 3 to 30 months with the mean age of 20 months. Analysis of the tumors revealed widespread aneuploidy and genetic instability, both hallmarks of nearly all solid tumors. Together with previous findings, our results indicate that Eg5 overexpression disrupts the unique balance of forces associated with normal spindle assembly and function, and thereby leads to the development of spindle defects, genetic instability, and tumors.
Additional
Information
in MTB
Tumor Records (59)
Strains (5)
Other
Accession
IDs
J:127104  Mouse Genome Informatics
17974955  National Library of Medicine/PubMed