title: Aurora B Overexpression Causes Aneuploidy and p21Cip1 Repression during Tumor Development.
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).
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: González-Loyola
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Fernández-Miranda
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Marianna
authors.initials: M
authors.lastname: Trakala
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Partida
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Samejima
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Histopathology Unit, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.affiliation: Histopathology Unit, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: de Martino
authors.affiliation: Cytogenetics Unit, M. D. Anderson Hospital, Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Martínez-Ramírez
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Cárcer
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez de Castro
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
authors.affiliation: Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain malumbres@cnio.es.
authors.forename: Marcos
authors.identifier: http://orcid.org/0000-0002-0829-6315
authors.initials: M
authors.lastname: Malumbres
mesh_terms: D000782:Aneuploidy; D000818:Animals; D064107:Aurora Kinase B / Q000502:physiology*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D008810:Mice, Inbred C57BL; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B