JCB logo
R&D Systems: New Poster Available
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
A correction to this article has been published: Dikovskaya et al., J. Cell Biol. 176 (3) 369
Published online
doi:10.1083/jcb.200610099
The Journal of Cell Biology, Vol. 176, No. 2, 183-195
The Rockefeller University Press, 0021-9525 $30.00
© Dikovskaya et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 5374K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Correction (v176,p369)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dikovskaya, D.
Right arrow Articles by Näthke, I. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dikovskaya, D.
Right arrow Articles by Näthke, I. S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
*Genetics Home Reference
Hazardous Substances DB
*TAXOL
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis



Dina Dikovskaya1, David Schiffmann1, Ian P. Newton1, Abigail Oakley1, Karin Kroboth1, Owen Sansom2, Thomas J. Jamieson2, Valerie Meniel3, Alan Clarke3, and Inke S. Näthke1

1 Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, Scotland, UK
2 Cancer Research UK, Beatson Laboratories, Glasgow G61 1BD, Scotland, UK
3 School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, UK

Correspondence to Inke S. Näthke: inke{at}lifesci.dundee.ac.uk

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show that inhibition of APC in U2OS cells compromises the mitotic spindle checkpoint. This is accompanied by a decrease in the association of the checkpoint proteins Bub1 and BubR1 with kinetochores. Additionally, APC depletion reduced apoptosis. As expected from this combination of defects, tetraploidy and polyploidy are consequences of APC inhibition in vitro and in vivo. The removal of APC produced the same defects in HCT116 cells that have constitutively active ß-catenin. These data show that the loss of APC immediately induces chromosomal instability as a result of a combination of mitotic and apoptotic defects. We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis.

Abbreviations used in this paper: APC, adenomatous polyposis coli; IQR, interquartile range; PE, phycoerythrin; RFP, red fluorescent protein; TCF, T cell factor.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents