Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes

G. Y. Gwak, J. H. Yoon, S. H. Lee, S. M. Lee, H. S. Lee, G. J. Gores

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) implicates that a compositional alteration in bile may contribute to the genesis of this cancer. Lysophosphatidylcholine (LPC) is generated in the bile of these patients. Given the role of cyclooxygenase-2 (COX-2) in biliary tract carcinogenesis, we postulated that LPC induces COX-2 in cholangiocytes. Methods: The effect of LPC on COX-2 expression in cholangiocytes was evaluated by immunoblot analysis, real-time PCR and reporter gene assay. Apoptosis was induced by TRAIL treatment, and quantified using DAPI staining. Results: Lysophosphatidylcholine increased COX-2 protein expression in cholangiocytes in a concentration- and time-dependent manner. LPC-induced Raf-1 activation was responsible for this COX-2 induction. Accordingly, LPC increased COX-2 mRNA levels in a Raf-1 dependent manner by stabilizing COX-2 mRNA. Finally, LPC attenuated TRAIL-mediated apoptosis through a COX-2/PgE2 dependent mechanism. Conclusions: Collectively, these results implicate that LPC inhibits cholangiocyte apoptosis by inducing COX-2 expression via a Raf-1 dependent mechanism. This anti-apoptotic signaling may participate in biliary tract carcinogenesis in APBDJ patients, and therefore, its interruption may be a viable chemopreventative strategy.

Original languageEnglish (US)
Pages (from-to)771-779
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume132
Issue number12
DOIs
StatePublished - Dec 1 2006

Keywords

  • Anomalous pancreaticobiliary ductal junction
  • Apoptosis
  • Biliary tract carcinoma
  • Cyclooxygenase-2
  • Lysophosphatidylcholine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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