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FASEB J. 2009 Aug;23(8):2741-8. doi: 10.1096/fj.09-130963. Epub 2009 Mar 30.

Deregulated Aurora-B induced tetraploidy promotes tumorigenesis.

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Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.


High expression of Aurora-B has been observed in various cancers, and inhibition of this kinase has been shown to halt cellular proliferation. However, the mechanism of effect of Aurora-B on cellular transformation has not been fully explored. Here, we show that overexpression of Aurora-B in murine epithelial cells promotes generation of tetraploids. In search of a related mechanism, spectral karyotyping was carried out, showing premature chromatid separation (PCS). Of interest, PCS is a hallmark of Robert's syndrome, which also involves cellular polyploidy and aneuploidy. Sorted tetraploid Aurora-B-overexpressing cells promoted significant mammary epithelial cancers when injected into nude mice, as compared to injection of nonfractionated cells, suggesting that tetraploidy is an important mediator of Aurora-B-induced tumorigenesis. Comparative chromosome hybridization performed on DNA derived from tetraploid cell-induced tumors indicates amplifications and deletions of regions throughout the genome, which include tumor-promoting or tumor-suppressing genes, respectively. Thus, sustained expression of Aurora-B induces tetraploidy, which, in turn, facilitates genomic instability and tumor development in a xenograft model.

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