Cargando…

Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53

Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle...

Descripción completa

Detalles Bibliográficos
Autores principales: Potapova, Tamara A., Seidel, Christopher W., Box, Andrew C., Rancati, Giulia, Li, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063615/
https://www.ncbi.nlm.nih.gov/pubmed/27559130
http://dx.doi.org/10.1091/mbc.E16-05-0268
_version_ 1782460013032243200
author Potapova, Tamara A.
Seidel, Christopher W.
Box, Andrew C.
Rancati, Giulia
Li, Rong
author_facet Potapova, Tamara A.
Seidel, Christopher W.
Box, Andrew C.
Rancati, Giulia
Li, Rong
author_sort Potapova, Tamara A.
collection PubMed
description Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute polyploidy was generated by knockdown of the essential regulator of cytokinesis anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target, CDK inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single cell–derived, adapted tetraploid clones showed up-regulation of several p53 target genes and cyclin D2, the activator of CDK4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results indicate that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis.
format Online
Article
Text
id pubmed-5063615
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-50636152016-12-30 Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53 Potapova, Tamara A. Seidel, Christopher W. Box, Andrew C. Rancati, Giulia Li, Rong Mol Biol Cell Articles Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute polyploidy was generated by knockdown of the essential regulator of cytokinesis anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target, CDK inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single cell–derived, adapted tetraploid clones showed up-regulation of several p53 target genes and cyclin D2, the activator of CDK4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results indicate that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis. The American Society for Cell Biology 2016-10-15 /pmc/articles/PMC5063615/ /pubmed/27559130 http://dx.doi.org/10.1091/mbc.E16-05-0268 Text en © 2016 Potapova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Potapova, Tamara A.
Seidel, Christopher W.
Box, Andrew C.
Rancati, Giulia
Li, Rong
Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title_full Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title_fullStr Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title_full_unstemmed Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title_short Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53
title_sort transcriptome analysis of tetraploid cells identifies cyclin d2 as a facilitator of adaptation to genome doubling in the presence of p53
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063615/
https://www.ncbi.nlm.nih.gov/pubmed/27559130
http://dx.doi.org/10.1091/mbc.E16-05-0268
work_keys_str_mv AT potapovatamaraa transcriptomeanalysisoftetraploidcellsidentifiescyclind2asafacilitatorofadaptationtogenomedoublinginthepresenceofp53
AT seidelchristopherw transcriptomeanalysisoftetraploidcellsidentifiescyclind2asafacilitatorofadaptationtogenomedoublinginthepresenceofp53
AT boxandrewc transcriptomeanalysisoftetraploidcellsidentifiescyclind2asafacilitatorofadaptationtogenomedoublinginthepresenceofp53
AT rancatigiulia transcriptomeanalysisoftetraploidcellsidentifiescyclind2asafacilitatorofadaptationtogenomedoublinginthepresenceofp53
AT lirong transcriptomeanalysisoftetraploidcellsidentifiescyclind2asafacilitatorofadaptationtogenomedoublinginthepresenceofp53