The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
Administrative Staff Authors  >
Administrative Staff Authors (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/33792

Title: Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells
Author: DUGGAN, SHANE
KELLEHER, DERMOT P
LONG, AIDEEN
Sponsor: Health Research Board
Higher Education Authority
Author's Homepage: http://people.tcd.ie/kellehdp
Keywords: Clinical Medicine
Issue Date: 2009
Publisher: BioMed Central
Citation: Looby E, Abdel-Latif MM, AthiĆ©-Morales V, Duggan S, Long A, Kelleher D. 'Deoxycholate induces COX-2 expression via Erk1/2 - p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells' BMC Cancer, (9), 190, 2009
Series/Report no.: BMC Cancer
9
190
Abstract: Background The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. Methods Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. Results DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. Conclusion DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.
Description: PUBLISHED
URI: http://dx.doi.org/10.1186/1471-2407-9-190
http://hdl.handle.net/2262/33792
Appears in Collections:Administrative Staff Authors (Scholarly Publications)

Files in This Item:

File Description SizeFormat
Deoxycholate induces COX-2 expression via Erk1 2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells.pdfpublished (publisher copy) peer-reviewed3.88 MBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback