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RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis

RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis

International Journal of Cancer 133(2): 275-285

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.

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Accession: 055333406

Download citation: RISBibTeXText

PMID: 23319376

DOI: 10.1002/ijc.28032

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