title: Activation of meiosis-specific genes is associated with depolyploidization of human tumor cells following radiation-induced mitotic catastrophe.
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 following exposure 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 division to produce smaller cells which are morphologically indistinguishable from control cells. Experiments conducted with the large-scale digital cell analysis system are discussed and 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. Although 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 promitotic to a promeiotic 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.
authors.affiliation: Department of Pathology, University of Iowa, Seamans Center, University of Iowa, Iowa City, Iowa, USA. fiorenza-ianzini@uiowa.edu
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Ianzini
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kosmacek
authors.forename: Elke S
authors.initials: ES
authors.lastname: Nelson
authors.forename: Eleonora
authors.initials: E
authors.lastname: Napoli
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Erenpreisa
authors.forename: Martins
authors.initials: M
authors.lastname: Kalejs
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mackey
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002467:Cell Nucleus / Q000528:radiation effects / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D008677:Metaphase / Q000235:genetics / Q000528:radiation effects; D008938:Mitosis / Q000235:genetics / Q000528:radiation effects*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D011123:Polyploidy
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C074556:DMC1 protein, human