English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells

Kuznetsova, A. Y., Seget, K., Moeller, G. K., de Pagter, M. S., de Roos, J. A. D. M., Dürrbaum, M., et al. (2015). Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. CELL CYCLE, 14(17), 2810-2820. doi:10.1080/15384101.2015.1068482.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Kuznetsova, Anastasia Y.1, Author           
Seget, Katarzyna1, Author           
Moeller, Giuliana K.1, Author           
de Pagter, Mirjam S.2, Author
de Roos, Jeroen A. D. M.2, Author
Dürrbaum, Milena1, Author           
Kuffer, Christian1, Author           
Mueller, Stefan2, Author
Zaman, Guido J. R.2, Author
Kloosterman, Wigard P.2, Author
Storchova, Zuzana1, Author           
Affiliations:
1Storchova, Zuzana / Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565171              
2external, ou_persistent22              

Content

show
hide
Free keywords: TUMOR-SUPPRESSOR; OXIDATIVE STRESS; MAMMALIAN-CELLS; ANEUPLOIDY; CANCER; CONSEQUENCES; FAILURE; GENE; OVEREXPRESSION; EVOLUTIONaneuploidy; cancer; CIN; drug resistance; p53; tetraploidy; whole genome doubling;
 Abstract: Up to 80% of human cancers, in particular solid tumors, contain cells with abnormal chromosomal numbers, or aneuploidy, which is often linked with marked chromosomal instability. Whereas in some tumors the aneuploidy occurs by missegregation of one or a few chromosomes, aneuploidy can also arise during proliferation of inherently unstable tetraploid cells generated by whole genome doubling from diploid cells. Recent findings from cancer genome sequencing projects suggest that nearly 40% of tumors underwent whole genome doubling at some point of tumorigenesis, yet its contribution to cancer phenotypes and benefits for malignant growth remain unclear. Here, we investigated the consequences of a whole genome doubling in both cancerous and non-transformed p53 positive human cells. SNP array analysis and multicolor karyotyping revealed that induced whole-genome doubling led to variable aneuploidy. We found that chromosomal instability (CIN) is a frequent, but not a default outcome of whole genome doubling. The CIN phenotypes were accompanied by increased tolerance to mitotic errors that was mediated by suppression of the p53 signaling. Additionally, the expression of pro-apoptotic factors, such as iASPP and cIAP2, was downregulated. Furthermore, we found that whole genome doubling promotes resistance to a broad spectrum of chemotherapeutic drugs and stimulates anchorage-independent growth even in non-transformed p53-positive human cells. Taken together, whole genome doubling provides multifaceted benefits for malignant growth. Our findings provide new insight why genome-doubling promotes tumorigenesis and correlates with poor survival in cancer.

Details

show
hide
Language(s): eng - English
 Dates: 2015
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CELL CYCLE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA : TAYLOR & FRANCIS INC
Pages: - Volume / Issue: 14 (17) Sequence Number: - Start / End Page: 2810 - 2820 Identifier: ISSN: 1538-4101