S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes
- Gwak, G-Y; Yoon, J-H; Lee, S-H; Lee, S-M; Lee, H-S; Gores, G J
- Issue Date
- Springer Verlag
- J Cancer Res Clin Oncol. 2006 Dec;132(12):771-9. Epub 2006 Jun 29.
- Animals; Apoptosis/*drug effects; Bile Ducts/cytology/metabolism; Cell Line, Tumor; Cyclooxygenase 2/*biosynthesis/*genetics; Dose-Response Relationship, Drug; Enzyme Induction/drug effects; Gene Expression Profiling; Humans; Lysophosphatidylcholines/*pharmacology; Male; Proto-Oncogene Proteins c-raf/*metabolism; RNA, Messenger/drug effects/genetics; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction
- 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.
- 0171-5216 (Print)
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