Skip Navigation


Carcinogenesis Advance Access originally published online on May 25, 2006
Carcinogenesis 2006 27(12):2371-2382; doi:10.1093/carcin/bgl071
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
27/12/2371    most recent
bgl071v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Bos, C. L.
Right arrow Articles by Richel, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bos, C. L.
Right arrow Articles by Richel, D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Protein phosphatase 2A is required for mesalazine-dependent inhibition of Wnt/ß-catenin pathway activity

Carina L. Bos1,2,*, Sander H. Diks3, James C.H. Hardwick1, Kimberley V. Walburg1, Maikel P. Peppelenbosch3 and Dick J. Richel2

1 Laboratory of Experimental Oncology and Radiobiology, University of Amsterdam The Netherlands
2 Department of Oncology, University of Amsterdam The Netherlands
3 Department of Cell Biology, University of Groningen The Netherlands

*To whom correspondence should be addressed at: Laboratory of Experimental Oncology and Radiobiology, G2-132, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5666034; Fax: +31 20 6977192; Email: carinaenjeroen{at}wanadoo.nl

The rising incidence and poor prognosis of colorectal cancer have aroused substantial interest in novel chemopreventive strategies. Interestingly, treatment of ulcerative colitis with mesalazine, which displays few side effects during long-term treatment, is associated with a reduced incidence of colorectal cancer, but its molecular mechanism is not known. The effect of mesalazine on the Wnt/ß-catenin pathway was studied in colorectal cancer cell lines to find a molecular basis underlying its chemopreventive features. Mesalazine affects the Wnt/ß-catenin pathway in adenomatous polyposis coli mutated cells with intact ß-catenin, judged by luciferase reporter assays. Furthermore, mesalazine treatment reduced expression of nuclear ß-catenin and Wnt/ß-catenin target genes, and increased ß-catenin phosphorylation. This effect on the Wnt/ß-catenin pathway is mediated via protein phosphatase 2A (PP2A): increased phosphorylation of PP2A after mesalazine treatment is observed, which coincides with decreased PP2A enzymatic activity. The inhibition of PP2A enzymatic activity by mesalazine is essential for its effect on the Wnt/ß-catenin pathway, as shown by transient transfection with siPP2A and mutant PP2A. This study shows, using concentrations of mesalazine identical to concentrations seen in patients with inflammatory bowel disease, that mesalazine inhibits the Wnt/ß-catenin pathway via inhibition of PP2A.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
C. Stolfi, D. Fina, R. Caruso, F. Caprioli, M. C. Fantini, A. Rizzo, M. Sarra, F. Pallone, and G. Monteleone
Mesalazine negatively regulates CDC25A protein expression and promotes accumulation of colon cancer cells in S phase
Carcinogenesis, June 1, 2008; 29(6): 1258 - 1266.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.