Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

Overview

Journal Science

Specialty Science

Date 2008 Nov 1

PMID 18974345

Citations 349

Authors

Bret R Williams

Vineet R Prabhu

Karen E Hunter

Christina M Glazier

Charles A Whittaker

David E Housman

Angelika Amon

Affiliations

Soon will be listed here.

Abstract

Aneuploidy, an incorrect number of chromosomes, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines, proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional copy of certain chromosomes. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells.

Citing Articles

DNA damage checkpoints balance a tradeoff between diploid- and polyploid-derived arrest failures.

Fujimaki K, Jambhekar A, Lahav G bioRxiv. 2025; .

PMID: 39990415 PMC: 11844538. DOI: 10.1101/2025.02.14.638318.

Proteogenomic analysis reveals adaptive strategies for alleviating the consequences of aneuploidy in cancer.

Bokenkamp J, Keuper K, Redel S, Barthel K, Johnson L, Becker A EMBO J. 2025; .

PMID: 39930267 DOI: 10.1038/s44318-025-00372-w.

Dynamics and regulatory roles of RNA mA methylation in unbalanced genomes.

Zhang S, Wang R, Luo K, Gu S, Liu X, Wang J Elife. 2025; 13.

PMID: 39853090 PMC: 11759410. DOI: 10.7554/eLife.100144.

Al Khazal F, Mahadev Bhat S, Zhu Y, de Araujo Correia C, Zhou S, Wilbanks B Cancer Metab. 2024; 12(1):39.

PMID: 39716277 PMC: 11668036. DOI: 10.1186/s40170-024-00369-9.

Preimplantation development analysis of aneuploid embryos with different chromosomal abnormalities.

Si K, Ma B, Bai J, Wu L, He H, Jin L Heliyon. 2024; 10(23):e40686.

PMID: 39687119 PMC: 11647804. DOI: 10.1016/j.heliyon.2024.e40686.

References

Segal D, McCoy E . Studies on Down's syndrome in tissue culture. I. Growth rates and protein contents of fibroblast cultures. J Cell Physiol. 1974; 83(1):85-90. DOI: 10.1002/jcp.1040830112. View

Niwa O, Tange Y, Kurabayashi A . Growth arrest and chromosome instability in aneuploid yeast. Yeast. 2006; 23(13):937-50. DOI: 10.1002/yea.1411. View

Weaver B, Silk A, Montagna C, Verdier-Pinard P, Cleveland D . Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2006; 11(1):25-36. DOI: 10.1016/j.ccr.2006.12.003. View

Rosner M, Kowalska A, Freilinger A, Prusa A, Marton E, Hengstschlager M . Cell cycle and cell size regulation in Down syndrome cells. J Neural Transm Suppl. 2004; (67):51-8. DOI: 10.1007/978-3-7091-6721-2_4. View

Toda T, Nakaseko Y, Niwa O, Yanagida M . Mapping of rRNA genes by integration of hybrid plasmids in Schizosaccharomyces pombe. Curr Genet. 2013; 8(2):93-7. DOI: 10.1007/BF00420224. View

Baker D, Jeganathan K, Cameron J, Thompson M, Juneja S, Kopecka A . BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet. 2004; 36(7):744-9. DOI: 10.1038/ng1382. View

Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, Saavedra E . Energy metabolism in tumor cells. FEBS J. 2007; 274(6):1393-418. DOI: 10.1111/j.1742-4658.2007.05686.x. View

ABERCROMBIE M . The bases of the locomotory behaviour of fibroblasts. Exp Cell Res. 1961; Suppl 8:188-98. DOI: 10.1016/0014-4827(61)90348-2. View

McCLINTOCK B . A Cytological and Genetical Study of Triploid Maize. Genetics. 1929; 14(2):180-222. PMC: 1201029. DOI: 10.1093/genetics/14.2.180. View

10.

Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe S . Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell. 2006; 11(1):9-23. PMC: 1850996. DOI: 10.1016/j.ccr.2006.10.019. View

11.

Sung H, Yeamans G, Ross C, Yasbin R . Roles of YqjH and YqjW, homologs of the Escherichia coli UmuC/DinB or Y superfamily of DNA polymerases, in stationary-phase mutagenesis and UV-induced mutagenesis of Bacillus subtilis. J Bacteriol. 2003; 185(7):2153-60. PMC: 151490. DOI: 10.1128/JB.185.7.2153-2160.2003. View

12.

Satge D, Sasco A, Lacour B . Are solid tumours different in children with Down's syndrome?. Int J Cancer. 2003; 106(2):297-8. DOI: 10.1002/ijc.11212. View

13.

Edlund T, Normark S . Recombination between short DNA homologies causes tandem duplication. Nature. 1981; 292(5820):269-71. DOI: 10.1038/292269a0. View

14.

Mao R, Zielke C, Zielke H, Pevsner J . Global up-regulation of chromosome 21 gene expression in the developing Down syndrome brain. Genomics. 2003; 81(5):457-67. DOI: 10.1016/s0888-7543(03)00035-1. View

15.

Shih I, Wang T, Traverso G, Romans K, Hamilton S, Kinzler K . Top-down morphogenesis of colorectal tumors. Proc Natl Acad Sci U S A. 2001; 98(5):2640-5. PMC: 30191. DOI: 10.1073/pnas.051629398. View

16.

Singh K, Multani D, Khush G . Secondary trisomics and telotrisomics of rice: origin, characterization, and use in determining the orientation of chromosome map. Genetics. 1996; 143(1):517-29. PMC: 1207283. DOI: 10.1093/genetics/143.1.517. View

17.

Todaro G, Green H . Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963; 17:299-313. PMC: 2106200. DOI: 10.1083/jcb.17.2.299. View

18.

Selmecki A, Forche A, Berman J . Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science. 2006; 313(5785):367-70. PMC: 1717021. DOI: 10.1126/science.1128242. View

19.

Ponder R, Fonville N, Rosenberg S . A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation. Mol Cell. 2005; 19(6):791-804. DOI: 10.1016/j.molcel.2005.07.025. View

20.

Larson P, De las Morenas A, Cerda S, Bennett S, Cupples L, Rosenberg C . Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors. J Pathol. 2006; 209(3):307-16. DOI: 10.1002/path.1973. View