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Mol Cell Biol. 2015 Oct;35(20):3566-78. doi: 10.1128/MCB.01286-14. Epub 2015 Aug 3.

Aurora B Overexpression Causes Aneuploidy and p21Cip1 Repression during Tumor Development.

Author information

1
Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
2
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
3
Histopathology Unit, Spanish National Cancer Research Center, Madrid, Spain.
4
Cytogenetics Unit, M. D. Anderson Hospital, Madrid, Spain.
5
Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain malumbres@cnio.es.

Abstract

Aurora kinase B, one of the three members of the mammalian Aurora kinase family, is the catalytic component of the chromosomal passenger complex, an essential regulator of chromosome segregation in mitosis. Aurora B is overexpressed in human tumors although whether this kinase may function as an oncogene in vivo is not established. Here, we report a new mouse model in which expression of the endogenous Aurkb locus can be induced in vitro and in vivo. Overexpression of Aurora B in cultured cells induces defective chromosome segregation and aneuploidy. Long-term overexpression of Aurora B in vivo results in aneuploidy and the development of multiple spontaneous tumors in adult mice, including a high incidence of lymphomas. Overexpression of Aurora B also results in a reduced DNA damage response and decreased levels of the p53 target p21(Cip1) in vitro and in vivo, in line with an inverse correlation between Aurora B and p21(Cip1) expression in human leukemias. Thus, overexpression of Aurora B may contribute to tumor formation not only by inducing chromosomal instability but also by suppressing the function of the cell cycle inhibitor p21(Cip1).

PMID:
26240282
PMCID:
PMC4573715
DOI:
10.1128/MCB.01286-14
[Indexed for MEDLINE]
Free PMC Article

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