Journal article
Activation of Meiosis-Specific Genes is Associated with Depolyploidization of Human Tumor Cells Following Radiation-Induced Mitotic Catastrophe
Cancer research (Chicago, Ill.), Vol.69(6), pp.2296-2304
03/15/2009
DOI: 10.1158/0008-5472.CAN-08-3364
PMCID: PMC2657811
PMID: 19258501
Abstract
Cancer is frequently characterized histologically by the appearance of large cells that are either aneuploid or polyploid. Aneuploidy and polyploidy are hallmarks of radiation-induced mitotic catastrophe (MC), a common phenomenon occurring in tumor cells with impaired p53 function exposed to various cytotoxic and genotoxic agents. MC is characterized by altered expression of mitotic regulators, untimely and abnormal cell division, delayed DNA damage, and changes in morphology. We report here that cells undergoing radiation-induced MC are more plastic with regards to ploidy and that this plasticity allows them to reorganize their genetic material through reduction divisions to produce smaller cells morphologically indistinguishable from control cells. Experiments conducted with the Large Scale Digital Cell Analysis System (LSDCAS) are discussed that show that a small fraction of polyploid cancer cells formed
via
radiation-induced MC can survive and start a process of depolyploidization that yields various outcomes. While most multipolar divisions failed and cell fusion occurred; some of these divisions were successful and originated a variety of cell progeny characterized by different ploidy. Among these ploidy phenotypes, a progeny of small mononucleated cells, indistinguishable from the untreated control cells, is often seen. We report here evidence that meiosis-specific genes are expressed in the polyploid cells during depolyploidization. Tumor cells might take advantage of the temporary change from a pro-mitotic to a pro-meiotic division regimen to facilitate depolyploidization and restore the proliferative state of the tumor cell population. These events might be mechanisms by which tumor progression and resistance to treatment occur
in vivo
.
Details
- Title: Subtitle
- Activation of Meiosis-Specific Genes is Associated with Depolyploidization of Human Tumor Cells Following Radiation-Induced Mitotic Catastrophe
- Creators
- Fiorenza Ianzini - Department of Pathology, University of Iowa, 500 Newton Road, Iowa City, IA, USAElizabeth A Kosmacek - Department of Pathology, University of Iowa, 500 Newton Road, Iowa City, IA, USAElke S Nelson - Department of Pathology, University of Iowa, 500 Newton Road, Iowa City, IA, USAEleonora Napoli - Department of Pathology, University of Iowa, 500 Newton Road, Iowa City, IA, USAJekaterina Erenpreisa - Latvia Biomedical Research and Study Centre, Ratsupites 1, Riga, LatviaMartins Kalejs - Latvia Biomedical Research and Study Centre, Ratsupites 1, Riga, LatviaMichael A Mackey - Department of Pathology, University of Iowa, 500 Newton Road, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.69(6), pp.2296-2304
- DOI
- 10.1158/0008-5472.CAN-08-3364
- PMID
- 19258501
- PMCID
- PMC2657811
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 03/15/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology
- Record Identifier
- 9984064557402771
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