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Published as doi: 10.1096/fj.09-130963.
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(The FASEB Journal. 2009;23:2741-2748.)
© 2009 FASEB

Deregulated Aurora-B induced tetraploidy promotes tumorigenesis

Hao G. Nguyen, Maria Makitalo, Dan Yang, Dharmaraj Chinnappan, Cynthia St. Hilaire and Katya Ravid1

Departments of Biochemistry and Medicine, Boston University School of Medicine, Boston, Massachusetts, USA

1 Correspondence: Department of Biochemistry, K225, Boston University School of Medicine, Boston, MA 02118, USA. E-mail: kravid{at}bu.edu

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.—Nguyen, H. G., Makitalo, M., Yang, D., Chinnappan, D., St. Hilaire, C., Ravid, K. Deregulated Aurora-B induced tetraploidy promotes tumorigenesis.


Key Words: polyploidy • cancer • cell cycle • premature chromatid separation






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