| RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of aurora-a and BRCA2 urian. | |
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MedLine Citation:
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PMID: 23319376 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. Over-expression of mutated RAS ablated BRCA2 expresson 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(FTβ)and insulin-like growth factor binding protein 3 (IGFBP-3). Our results suggest that the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigensis. © 2013 Wiley Periodicals, Inc. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-15 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: - ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2013 UICC. |
Affiliation:
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Cancer Research Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China; Departments of Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. yanggong@fudan.edu.cn. |
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