Document Detail


Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation.
MedLine Citation:
PMID:  21250945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
'Neosis' describes the process whereby p53 function-deficient tumour cells undergo self-renewal after genotoxic damage apparently via senescing ETCs (endopolyploid tumour cells). We previously reported that autophagic digestion and extrusion of DNA occurs in ETC and subsequently revealed that self-renewal transcription factors are also activated under these conditions. Here, we further studied this phenomenon in a range of cell lines after genotoxic damage induced by gamma irradiation, ETO (etoposide) or PXT (paclitaxel) treatment. These experiments revealed that chromatin degradation by autophagy was compatible with continuing mitotic activity in ETC. While the actively polyploidizing primary ETC produced early after genotoxic insult activated self-renewal factors throughout the polygenome, the secondary ETC restored after failed multipolar mitosis underwent subnuclei differentiation. As such, only a subset of subnuclei continued to express OCT4 and NANOG, while those lacking these factors stopped DNA replication and underwent degradation and elimination through autophagy. The surviving subnuclei sequestered nascent cytoplasm to form subcells, while being retained within the confines of the old ETC. Finally, the preformed paradiploid subcells became released from their linking chromosome bridges through autophagy and subsequently began cell divisions. These data show that 'neotic' ETC resulting from genotoxically damaged p53 function-deficient tumour cells develop through a heteronuclear system differentiating the polyploid genome into rejuvenated 'viable' subcells (which provide mitotically propagating paradiploid descendents) and subnuclei, which become degraded and eliminated by autophagy. The whole process reduces aneuploidy in descendants of ETC.
Authors:
Jekaterina Erenpreisa; Kristine Salmina; Anda Huna; Elizabeth A Kosmacek; Mark S Cragg; Fiorenza Ianzini; Alim P Anisimov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell biology international     Volume:  35     ISSN:  1095-8355     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-20     Completed Date:  2011-10-03     Revised Date:  2012-08-02    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  687-95     Citation Subset:  IM    
Affiliation:
Latvian Biomedical Centre, Ratsupites 1, Riga, Latvia. katrina@biomed.lu.lv
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MeSH Terms
Descriptor/Qualifier:
Autophagy* / drug effects,  radiation effects
Cell Line, Tumor
Chromatin / genetics,  metabolism*
Chromatin Assembly and Disassembly
DNA Fragmentation* / drug effects,  radiation effects
DNA Replication* / drug effects,  radiation effects
Etoposide / pharmacology
Gamma Rays / adverse effects
Genome, Human
Homeodomain Proteins / genetics,  metabolism
Humans
Mitosis
Neoplasms / genetics*,  metabolism,  pathology
Octamer Transcription Factor-3 / genetics,  metabolism
Paclitaxel / pharmacology
Ploidies*
Tumor Suppressor Protein p53 / deficiency*,  genetics
Grant Support
ID/Acronym/Agency:
CA/GM94801/CA/NCI NIH HHS; CA86862/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Chromatin; 0/Homeodomain Proteins; 0/NANOG protein, human; 0/Octamer Transcription Factor-3; 0/POU5F1 protein, human; 0/Tumor Suppressor Protein p53; 33069-62-4/Paclitaxel; 33419-42-0/Etoposide
Comments/Corrections
Erratum In:
Cell Biol Int. 2011 Aug 1;35(8):869

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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