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Deregulated Aurora‐B induced tetraploidy promotes tumorigenesis
Author(s) -
Nguyen Hao G.,
Makitalo Maria,
Yang Dan,
Chinnappan Dharmaraj,
St.Hilaire Cynthia,
Ravid Katya
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-130963
Subject(s) - carcinogenesis , biology , chromosome instability , genome instability , chromatid , cancer research , aurora inhibitor , microbiology and biotechnology , karyotype , chromosome , cell , genetics , gene , cell cycle , dna , dna damage
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 aneu‐ ploidy. 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 tumorsuppressing 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. FASEBJ. 23, 2741–2748 (2009)