Abstract
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.
Original language | English (US) |
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Pages (from-to) | 275-285 |
Number of pages | 11 |
Journal | International Journal of Cancer |
Volume | 133 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2013 |
Keywords
- Aurora-A
- BRCA2
- RAS
- cytokinesis
- genomic instability
- polyploid cancer cells
ASJC Scopus subject areas
- Oncology
- Cancer Research