Endopolyploidy in irradiated p53-deficient tumour cell lines: persistence of cell division activity in giant cells expressing Aurora-B kinase.
Wheatley, Sally P
Kosmacek, Elizabeth A
Anisimov, Alim P
Davis, Paul J
Illidge, Timothy M
AffiliationLatvia Biomedicine Research and Study Centre, Riga, Latvia. email@example.com
MetadataShow full item record
AbstractRecent findings including computerised live imaging suggest that polyploidy cells transiently emerging after severe genotoxic stress (and named 'endopolyploid cells') may have a role in tumour regrowth after anti-cancer treatment. Until now, mostly the factors enabling metaphase were studied in them. Here we investigate the mitotic activities and the role of Aurora-B, in view of potential depolyploidisation of these cells, because Aurora-B kinase is responsible for coordination and completion of mitosis. We observed that endopolyploid giant cells are formed via different means in irradiated p53 tumours, by: (1) division/fusion of daughter cells creating early multi-nucleated cells; (2) asynchronous division/fusion of sub-nuclei of these multi-nucleated cells; (3) a series of polyploidising mitoses reverting replicative interphase from aborted metaphase and forming giant cells with a single nucleus; (4) micronucleation of arrested metaphases enclosing genome fragments; or (5) incomplete division in the multi-polar mitoses forming late multi-nucleated giant cells. We also observed that these activities can release para-diploid cells, although infrequently. While apoptosis typically occurs after a substantial delay in these cells, we also found that approximately 2% of the endopolyploid cells evade apoptosis and senescence arrest and continue some form of mitotic activity. We describe here that catalytically active Aurora-B kinase is expressed in the nuclei of many endopolyploid cells in interphase, as well as being present at the centromeres, mitotic spindle and cleavage furrow during their attempted mitotes. The totally micronucleated giant cells (containing sub-genomic fragments in multiple micronuclei) represented only the minor fraction which failed to undergo mitosis, and Aurora-B was absent from it. These observations suggest that most endopolyploid tumour cells are not reproductively inert and that Aurora-B may contribute to the establishment of resistant tumours post-irradiation.
CitationEndopolyploidy in irradiated p53-deficient tumour cell lines: persistence of cell division activity in giant cells expressing Aurora-B kinase. 2008, 32 (9):1044-56 Cell Biol. Int.
JournalCell Biology International
- Volume increase and spatial shifts of chromosome territories in nuclei of radiation-induced polyploidizing tumour cells.
- Authors: Schwarz-Finsterle J, Scherthan H, Huna A, González P, Mueller P, Schmitt E, Erenpreisa J, Hausmann M
- Issue date: 2013 Aug 30
- Segregation of genomes in polyploid tumour cells following mitotic catastrophe.
- Authors: Erenpreisa J, Kalejs M, Ianzini F, Kosmacek EA, Mackey MA, Emzinsh D, Cragg MS, Ivanov A, Illidge TM
- Issue date: 2005 Dec
- The active form of the metabolic sensor: AMP-activated protein kinase (AMPK) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis.
- Authors: Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA
- Issue date: 2009 Aug
- Aurora-B dysfunction of multinucleated giant cells in glioma detected by site-specific phosphorylated antibodies.
- Authors: Fujita M, Mizuno M, Nagasaka T, Wakabayashi T, Maeda K, Ishii D, Arima T, Kawajiri A, Inagaki M, Yoshida J
- Issue date: 2004 Dec
- The absence of p53 aggravates polyploidy and centrosome number abnormality induced by Aurora-C overexpression.
- Authors: Dutertre S, Hamard-Péron E, Cremet JY, Thomas Y, Prigent C
- Issue date: 2005 Dec