Carcinogenesis Advance Access published online on December 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgh010
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARCINOGENESIS
1 Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021
* Corresponding author. E-mail: olga_tucker{at}hotmail.com.
Received 2 April 2003
; revised 30 September 2003
; accepted 27 October 2003
To investigate a possible link between bile acids and the pathogenesis of pancreatic cancer, we determined whether conjugated or unconjugated bile acids induced COX-2 in two human pancreatic cancer cell lines, BxPC-3 and SU 86.86. Bile acids are known promoters of gastric and colon cancer. We previously demonstrated that cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in human pancreatic adenocarcinoma. Both human pancreatic cell lines were treated with conjugated and unconjugated bile acids. COX-2 mRNA and protein were determined. In addition, PGE2 synthesis was measured. Treatment with conjugated or unconjugated bile acids for 3h up-regulated COX-2 mRNA. Chenodeoxycholate or deoxycholate at concentrations ranging from 12.5µM-100µM caused a dose-dependent induction of COX-2 protein with a maximal effect at 100µM. Induction of COX-2 protein by chenodeoxycholate and deoxycholate was detected after treatment for 6h with maximal induction at 12h. Taurochenodeoxycholate, a conjugated bile acid, also caused dose-dependent induction of COX-2 but higher concentrations of bile acid (200µM-1200µM) were required. Levels of COX-1 were unaffected by bile acid treatment. Unconjugated and conjugated bile acids caused 7-fold and 4-fold increases in PGE2 production, respectively. Taken together, these findings suggest a possible role for bile acids in the pathogenesis of pancreatic cancer.
Bile acids, cyclooxygenase-1, cyclooxygenase-2, prostaglandins, pancreatic cancer
Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines
2 Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021; Department of Medicine, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021; Strang Cancer Prevention Center, New York, NY 10021
3 Department of Medicine, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021; Strang Cancer Prevention Center, New York, NY 10021
4 Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021; Strang Cancer Prevention Center, New York, NY 10021
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Miyaki, P. Yang, H.-H. Tai, K. Subbaramaiah, and A. J. Dannenberg Bile acids inhibit NAD+-dependent 15-hydroxyprostaglandin dehydrogenase transcription in colonocytes Am J Physiol Gastrointest Liver Physiol, September 1, 2009; 297(3): G559 - G566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Song, S. Guha, K. Liu, N. S Buttar, and R. S Bresalier COX-2 induction by unconjugated bile acids involves reactive oxygen species-mediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma Gut, November 1, 2007; 56(11): 1512 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Meng, S. Ceryak, Z. Aratsu, L. Jones, L. Epstein, and B. Bouscarel Biphasic regulation by bile acids of dermal fibroblast proliferation through regulation of cAMP production and COX-2 expression level Am J Physiol Cell Physiol, September 1, 2006; 291(3): C546 - C554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Silva, S. Dasgupta, G. Wang, K. Krishnamurthy, E. Ritter, and E. Bieberich Lipids isolated from bone induce the migration of human breast cancer cells J. Lipid Res., April 1, 2006; 47(4): 724 - 733. [Abstract] [Full Text] [PDF]
|
|