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, Gregory James Gores

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 2006

Fingerprint

Lysophosphatidylcholines
Cyclooxygenase 2
Cell Death
Biliary Tract
Apoptosis
Bile
Carcinogenesis
Messenger RNA
Reporter Genes
Real-Time Polymerase Chain Reaction
Staining and Labeling
Carcinoma
Incidence

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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, Gregory James.

In: Journal of Cancer Research and Clinical Oncology, Vol. 132, No. 12, 12.2006, p. 771-779.

Research output: Contribution to journalArticle

@article{85fb559f58fd487e8de6e553391c0105,
title = "Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes",
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.",
keywords = "Anomalous pancreaticobiliary ductal junction, Apoptosis, Biliary tract carcinoma, Cyclooxygenase-2, Lysophosphatidylcholine",
author = "Gwak, {G. Y.} and Yoon, {J. H.} and Lee, {S. H.} and Lee, {S. M.} and Lee, {H. S.} and Gores, {Gregory James}",
year = "2006",
month = "12",
doi = "10.1007/s00432-006-0125-5",
language = "English (US)",
volume = "132",
pages = "771--779",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "12",

}

TY - JOUR

T1 - Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes

AU - Gwak, G. Y.

AU - Yoon, J. H.

AU - Lee, S. H.

AU - Lee, S. M.

AU - Lee, H. S.

AU - Gores, Gregory James

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - Anomalous pancreaticobiliary ductal junction

KW - Apoptosis

KW - Biliary tract carcinoma

KW - Cyclooxygenase-2

KW - Lysophosphatidylcholine

UR - http://www.scopus.com/inward/record.url?scp=33749482834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749482834&partnerID=8YFLogxK

U2 - 10.1007/s00432-006-0125-5

DO - 10.1007/s00432-006-0125-5

M3 - Article

C2 - 16810500

AN - SCOPUS:33749482834

VL - 132

SP - 771

EP - 779

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 12

ER -