Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo Journal Article

   

Authors:	Diaz-Rodríguez, E.; Sotillo, R.; Schvartzman, J. M.; Benezra, R.
Article Title:	Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo
Abstract:	Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here that the overexpression of Hec1 in an inducible mouse model results in mitotic checkpoint hyperactivation. As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy. These results underscore the role of chromosomal instability as a result of mitotic checkpoint hyperactivation in the initiation of tumorigenesis. © 2008 by The National Academy of Sciences of the USA.
Keywords:	controlled study; protein expression; unclassified drug; human cell; liver cell carcinoma; nonhuman; cancer grading; neoplasms; mitosis; mouse; animals; cell cycle proteins; mice; gene overexpression; embryo; animal experiment; animal model; genotype; in vivo study; enzyme activation; carcinogenesis; transgenic mouse; mice, transgenic; nuclear proteins; sarcoma; gene expression regulation; tissue distribution; prostate tumor; membrane protein; lymphoma; immunoblotting; fibroblast; chromosomal instability; real time polymerase chain reaction; doxycycline; intestine tumor; lymphocyte; aneuploidy; southern blotting; protein mad2; kinetochores; lung adenoma; chromosome instability; bub3 protein; highly expressed in cancer 1 protein
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	105
Issue:	43
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2008-10-28
Start Page:	16719
End Page:	16724
Language:	English
DOI:	10.1073/pnas.0803504105
PUBMED:	18940925
PROVIDER:	scopus
PMCID:	PMC2570608
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-55949096605&partnerID=40&md5=cf3b506533ef19e0dcf3b989fadc98f6
Notes:	--- - "Cited By (since 1996): 29" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/14294