Skip Navigation



Carcinogenesis Advance Access published online on January 19, 2008
Carcinogenesis, doi:10.1093/carcin/bgn004
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
29/4/849    most recent
bgn004v1
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 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 arrowRequest Permissions
Google Scholar
Right arrow Articles by Clemo, N. K
Right arrow Articles by Williams, A. C
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clemo, N. K
Right arrow Articles by Williams, A. C
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-{kappa}B activity

Nadine K Clemo1, Tracey J Collard1, Samantha Southern1, Kieron D Edwards2, Moganaden Moorghen3, Graham Packham4, Angela Hague5, Christos Paraskeva1 and Ann C Williams1

1 Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
2 Institute of Molecular Plant Sciences, University of Edinburgh, Edinburgh, United Kingdom
3 Department of Pathology and Histology, Bristol Royal Infirmary, Bristol, United Kingdom
4 Cancer Research UK Clinical Centre, Cancer Sciences Division, University of Southampton, UK
5 Department of Oral and Dental Science, University of Bristol, Bristol, United Kingdom

Correspondence: A.C.Williams{at}bris.ac.uk

Although expression of the anti-apoptotic protein BAG-1 has been reported as up-regulated in a number of malignancies, we show for the first time that BAG-1 is over-expressed in medium/large sized colorectal adenomas and carcinomas compared to normal epithelium. To investigate whether expression of BAG-1 is important for colorectal tumour cell survival, microarray analysis was carried out on the HCT116 colorectal carcinoma cell line following transfection with BAG-1 siRNA. Analysis identified altered expression of a subset of potential NF-{kappa}B regulated genes. Furthermore, knockdown of BAG-1 was shown to inhibit NF-{kappa}B transcriptional activity. Inhibition of NF-{kappa}B activity using BAG-1 siRNA or the NF-{kappa}B inhibitor BAY-117082 suppressed HCT116 cell yield and induced apoptosis; combined treatment had no additive effect, suggesting that the decrease in cell yield associated with knockdown of BAG-1 expression is mediated via inhibition of NF-{kappa}B. Of clinical relevance, BAG-1 siRNA sensitised colorectal carcinoma cells to apoptosis induced by potential therapeutic agent TRAIL as well as TNF-{alpha}, both inducers of NF-{kappa}B activity. In summary, knockdown of BAG-1 leads to inhibition of NF-{kappa}B, identifying BAG-1 as a novel regulator of NF-{kappa}B. It is proposed that, by inhibiting NF-{kappa}B, suppression of BAG-1 could represent a novel strategy to impede colorectal cancer cell survival and as an adjuvant, increase sensitivity to current therapeutic regimes.

Key Words: BAG-1 • colorectal • NF-{kappa}B • TNF-{alpha} • apoptosis

Received October 10, 2007; revised December 17, 2007; accepted December 27, 2007.


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
 J. Pharmacol. Exp. Ther.Home page
A. Sharp, S. J. Crabb, P. W. M. Johnson, A. Hague, R. Cutress, P. A. Townsend, A. Ganesan, and G. Packham
Thioflavin S (NSC71948) Interferes with Bcl-2-Associated Athanogene (BAG-1)-Mediated Protein-Protein Interactions
J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 680 - 689.
[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.