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A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells

BACKGROUND: Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instabi...

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Autores principales: Roh, Meejeon, Franco, Omar E., Hayward, Simon W., van der Meer, Riet, Abdulkadir, Sarki A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440349/
https://www.ncbi.nlm.nih.gov/pubmed/18596907
http://dx.doi.org/10.1371/journal.pone.0002572
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author Roh, Meejeon
Franco, Omar E.
Hayward, Simon W.
van der Meer, Riet
Abdulkadir, Sarki A.
author_facet Roh, Meejeon
Franco, Omar E.
Hayward, Simon W.
van der Meer, Riet
Abdulkadir, Sarki A.
author_sort Roh, Meejeon
collection PubMed
description BACKGROUND: Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells. PRINCIPAL FINDINGS: When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo. CONCLUSIONS: Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells.
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spelling pubmed-24403492008-07-02 A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells Roh, Meejeon Franco, Omar E. Hayward, Simon W. van der Meer, Riet Abdulkadir, Sarki A. PLoS One Research Article BACKGROUND: Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells. PRINCIPAL FINDINGS: When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo. CONCLUSIONS: Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells. Public Library of Science 2008-07-02 /pmc/articles/PMC2440349/ /pubmed/18596907 http://dx.doi.org/10.1371/journal.pone.0002572 Text en Roh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roh, Meejeon
Franco, Omar E.
Hayward, Simon W.
van der Meer, Riet
Abdulkadir, Sarki A.
A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title_full A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title_fullStr A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title_full_unstemmed A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title_short A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells
title_sort role for polyploidy in the tumorigenicity of pim-1-expressing human prostate and mammary epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440349/
https://www.ncbi.nlm.nih.gov/pubmed/18596907
http://dx.doi.org/10.1371/journal.pone.0002572
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