title: Deregulated Aurora-B induced tetraploidy promotes tumorigenesis.
abstract: 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.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Hao G
authors.initials: HG
authors.lastname: Nguyen
authors.forename: Maria
authors.initials: M
authors.lastname: Makitalo
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Dharmaraj
authors.initials: D
authors.lastname: Chinnappan
authors.forename: Cynthia
authors.initials: C
authors.lastname: St Hilaire
authors.forename: Katya
authors.initials: K
authors.lastname: Ravid