Journal article
Endopolyploidy in irradiated p53-deficient tumour cell lines: Persistence of cell division activity in giant cells expressing Aurora-B kinase
Cell biology international, Vol.32(9), pp.1044-1056
2008
DOI: 10.1016/j.cellbi.2008.06.003
PMCID: PMC2570184
PMID: 18602486
Abstract
Recent 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 ∼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.
Details
- Title: Subtitle
- Endopolyploidy in irradiated p53-deficient tumour cell lines: Persistence of cell division activity in giant cells expressing Aurora-B kinase
- Creators
- Jekaterina Erenpreisa - Latvia Biomedicine Research and Study Centre, Riga, LatviaAndrei Ivanov - Paterson Institute for Cancer Research, Manchester, UKSally P Wheatley - Genome Damage and Stability Centre, Sussex University, Brighton, UKElizabeth A Kosmacek - University of Iowa, Iowa City, IA, USAFiorenza Ianzini - University of Iowa, Iowa City, IA, USAAlim P Anisimov - Far-East State University, Vladivostok, Russian FederationMichael Mackey - University of Iowa, Iowa City, IA, USAPaul J Davis - University of Iowa, Iowa City, IA, USAGrigorijs Plakhins - Latvia Biomedicine Research and Study Centre, Riga, LatviaTimothy M Illidge - Paterson Institute for Cancer Research, Manchester, UK
- Resource Type
- Journal article
- Publication Details
- Cell biology international, Vol.32(9), pp.1044-1056
- DOI
- 10.1016/j.cellbi.2008.06.003
- PMID
- 18602486
- PMCID
- PMC2570184
- NLM abbreviation
- Cell Biol Int
- ISSN
- 1065-6995
- eISSN
- 1095-8355
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology
- Record Identifier
- 9984064218902771
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