Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition Journal Article

   

Authors:	Schvartzman, J. M.; Duijf, P.; Sotillo, R.; Coker, C.; Benezra, R.
Article Title:	Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition
Abstract:	Multiple mechanisms have been proposed to explain how Rb and p53 tumor suppressor loss lead to chromosome instability (CIN). It was recently shown that Rb pathway inhibition causes overexpression of the mitotic checkpoint gene Mad2, but whether Mad2 overexpression is required to generate CIN in this context is unknown. Here, we show that CIN in cultured cells lacking Rb family proteins requires Mad2 upregulation and that this upregulation is also necessary for CIN and tumor progression in vivo. Mad2 is also repressed by p53 and its upregulation is required for CIN in a p53 mutant tumor model. These results demonstrate that Mad2 overexpression is a critical mediator of the CIN observed upon inactivation of two major tumor suppressor pathways. © 2011 Elsevier Inc.
Keywords:	controlled study; nonhuman; animal cell; mouse; animal experiment; animal model; in vivo study; in vitro study; protein p53; cell culture; chromosomal instability; upregulation; tumor growth; breast adenocarcinoma; retinoblastoma protein; anaplastic carcinoma; mediator; protein mad2
Journal Title:	Cancer Cell
Volume:	19
Issue:	6
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2011-06-14
Start Page:	701
End Page:	714
Language:	English
DOI:	10.1016/j.ccr.2011.04.017
PROVIDER:	scopus
PMCID:	PMC3120099
PUBMED:	21665145
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79958733630&partnerID=40&md5=c3d5a6865cb7a6fecf3cc955602e8b73
Notes:	--- - "Export Date: 17 August 2011" - "CODEN: CCAEC" - "Source: Scopus"

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