Document Detail


RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis.
MedLine Citation:
PMID:  23319376     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood. To better understand how RAS functions, we measured the activity of the functionally related genes Aurora-A and BRCA2 in ovarian cancer cell lines and tumor samples containing RAS mutations. We found that Aurora-A and BRCA2 inversely controlled RAS-associated genomic instability and ovarian tumorigenesis through regulation of cytokinesis and polyploidization. Overexpression of mutated RAS ablated BRCA2 expression but induced Aurora-A accumulation at the midbody, leading to abnormal cytokinesis and ultimately chromosomal instability via polyploidy in cancer cells. RAS regulates the expression of Aurora-A and BRCA2 through dysregulated protein expression of farnesyl protein transferase β and insulin-like growth factor binding protein 3. Our results suggest that the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigenesis.
Authors:
Gong Yang; Imelda Mercado-Uribe; Asha S Multani; Subrata Sen; Ie-Ming Shih; Kwong-Kwok Wong; David M Gershenson; Jinsong Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-12
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-05-15     Completed Date:  2013-07-11     Revised Date:  2014-01-08    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Alkyl and Aryl Transferases / metabolism
Animals
Aurora Kinase A
Aurora Kinases
BRCA2 Protein / metabolism*
Cell Line, Tumor
Cytogenetics
Cytokinesis
Female
Gene Expression Regulation, Neoplastic*
Genomic Instability
Humans
Immunohistochemistry
Insulin-Like Growth Factor Binding Protein 3 / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Mutation
Neoplasm Transplantation
Ovarian Neoplasms / metabolism*
Protein-Serine-Threonine Kinases / metabolism*
ras Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
1R01CA131183-01A2/CA/NCI NIH HHS; CA016672/CA/NCI NIH HHS; IP50CA83638/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; P50 CA083639/CA/NCI NIH HHS; R01 CA131183/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BRCA2 Protein; 0/BRCA2 protein, human; 0/Insulin-Like Growth Factor Binding Protein 3; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/p21(ras) farnesyl-protein transferase; EC 2.7.11.1/Aurka protein, mouse; EC 2.7.11.1/Aurora Kinase A; EC 2.7.11.1/Aurora Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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