Send to

Choose Destination
See comment in PubMed Commons below
Gastroenterology. 2002 Apr;122(4):985-93.

Bile acids induce cyclooxygenase-2 expression via the epidermal growth factor receptor in a human cholangiocarcinoma cell line.

Author information

Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota 55905, USA.



Although bile acids have been implicated in colon cancer development, their role in biliary tract carcinogenesis remains unexplored. Because receptor tyrosine kinases and cyclooxygenase (COX)-2 have been implicated in carcinogenesis, we examined the hypothesis that bile acids modulate these enzymes in KMBC cells, a human cholangiocarcinoma cell line.


The effect of bile acids on epidermal growth factor receptor (EGFR) stimulation, mitogen-activated protein kinase (MAPK) activation, and COX-2 expression was evaluated.


Bile acids both induced EGFR phosphorylation and enhanced COX-2 protein expression. Bile acid-induced EGFR phosphorylation was associated with subsequent activation of MAPK p42/44, p38, and c-Jun-N-terminal kinase (JNK). The MAPK inhibitors, PD098059 for MAP or extracellular signal-regulated kinase 1, SB203580 for p38, and BAY 37-9751 for Raf-1, blocked COX-2 induction by bile acids. However, inhibition of JNK activity did not block bile acid-mediated COX-2 induction.


The results show that EGFR is activated by bile acids and functions to induce COX-2 expression by an MAPK cascade. This induction of COX-2 may participate in the genesis and progression of cholangiocarcinomas.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center