Cargando…
Proliferation of aneuploid human cells is limited by a p53-dependent mechanism
Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid ce...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819684/ https://www.ncbi.nlm.nih.gov/pubmed/20123995 http://dx.doi.org/10.1083/jcb.200905057 |
_version_ | 1782177301209808896 |
---|---|
author | Thompson, Sarah L. Compton, Duane A. |
author_facet | Thompson, Sarah L. Compton, Duane A. |
author_sort | Thompson, Sarah L. |
collection | PubMed |
description | Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid cells is compromised by chromosome missegregation. The mechanism for this intolerance of nondiploid genomes is unknown. In this study, we show that in otherwise diploid human cells, chromosome missegregation causes a cell cycle delay with nuclear accumulation of the tumor suppressor p53 and the cyclin kinase inhibitor p21. Deletion of the p53 gene permits the accumulation of nondiploid cells such that CIN generates cells with aneuploid genomes that resemble many human tumors. Thus, the p53 pathway plays an important role in limiting the propagation of aneuploid human cells in culture to preserve the diploid karyotype of the population. These data fit with the concordance of aneuploidy and disruption of the p53 pathway in many tumors, but the presence of aneuploid cells in some normal human and mouse tissues indicates that there are known exceptions to the involvement of p53 in aneuploid cells and that tissue context may be important in how cells respond to aneuploidy. |
format | Text |
id | pubmed-2819684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28196842010-08-08 Proliferation of aneuploid human cells is limited by a p53-dependent mechanism Thompson, Sarah L. Compton, Duane A. J Cell Biol Research Articles Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid cells is compromised by chromosome missegregation. The mechanism for this intolerance of nondiploid genomes is unknown. In this study, we show that in otherwise diploid human cells, chromosome missegregation causes a cell cycle delay with nuclear accumulation of the tumor suppressor p53 and the cyclin kinase inhibitor p21. Deletion of the p53 gene permits the accumulation of nondiploid cells such that CIN generates cells with aneuploid genomes that resemble many human tumors. Thus, the p53 pathway plays an important role in limiting the propagation of aneuploid human cells in culture to preserve the diploid karyotype of the population. These data fit with the concordance of aneuploidy and disruption of the p53 pathway in many tumors, but the presence of aneuploid cells in some normal human and mouse tissues indicates that there are known exceptions to the involvement of p53 in aneuploid cells and that tissue context may be important in how cells respond to aneuploidy. The Rockefeller University Press 2010-02-08 /pmc/articles/PMC2819684/ /pubmed/20123995 http://dx.doi.org/10.1083/jcb.200905057 Text en © 2010 Thompson and Compton This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Thompson, Sarah L. Compton, Duane A. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title | Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title_full | Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title_fullStr | Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title_full_unstemmed | Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title_short | Proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
title_sort | proliferation of aneuploid human cells is limited by a p53-dependent mechanism |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819684/ https://www.ncbi.nlm.nih.gov/pubmed/20123995 http://dx.doi.org/10.1083/jcb.200905057 |
work_keys_str_mv | AT thompsonsarahl proliferationofaneuploidhumancellsislimitedbyap53dependentmechanism AT comptonduanea proliferationofaneuploidhumancellsislimitedbyap53dependentmechanism |