Protease-activated receptor-2 regulates cyclooxygenase-2 expression in human bile duct cancer via the pathways of mitogen-activated protein kinases and nuclear factor kappa B

Hidetoshi Eguchi, Kentaro Iwaki, Kohei Shibata, Tadashi Ogawa, Masayuki Ohta, Seigo Kitano

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background/purpose: Recent studies have suggested that protease-activated receptor-2 (PAR-2) activity correlates with cell proliferation and tumor growth, and its activation induces expression of cyclooxygenase-2 (COX-2). However, no previous reports have investigated PAR-2 signaling pathways in bile duct cancer. The aim of this study was to determine whether PAR-2 activation can regulate COX-2 expression via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) in human bile duct cancer cells. Methods: We immunohistochemically examined PAR-2 and COX-2 expression in 104 resected human specimens of extrahepatic bile duct cancer. We then determined how inhibitors of MAPKs and NF-κB signaling pathways influence COX-2 expression under PAR-2 activation in HuCCT1 and TKKK, human bile duct cancer cell lines. Results: PAR-2 and COX-2 proteins were immunohistochemically recognized in 63 and 57% of specimens and were significantly correlated. PAR-2 agonist peptide activated mRNA and protein expression of COX-2 in HuCCT1 and TKKK. Pharmacologic blockade of p44/42 or p38 MAPK significantly inhibited PAR-2-activated mRNA and protein expression of COX-2 in both cells. COX-2 protein expression was also inhibited by the blocker of NF-κB pathway in both cells. Conclusions: PAR-2 may regulate COX-2 expression in human bile duct cancer via the MAPKs and NF-κB pathways.

Original languageEnglish
Pages (from-to)147-153
Number of pages7
JournalJournal of Hepato-Biliary-Pancreatic Sciences
Volume18
Issue number2
DOIs
Publication statusPublished - Mar 1 2011

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PAR-2 Receptor
Bile Duct Neoplasms
NF-kappa B
Cyclooxygenase 2
Mitogen-Activated Protein Kinases
Proteins
Extrahepatic Bile Ducts
Messenger RNA
p38 Mitogen-Activated Protein Kinases
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Protease-activated receptor-2 regulates cyclooxygenase-2 expression in human bile duct cancer via the pathways of mitogen-activated protein kinases and nuclear factor kappa B. / Eguchi, Hidetoshi; Iwaki, Kentaro; Shibata, Kohei; Ogawa, Tadashi; Ohta, Masayuki; Kitano, Seigo.

In: Journal of Hepato-Biliary-Pancreatic Sciences, Vol. 18, No. 2, 01.03.2011, p. 147-153.

Research output: Contribution to journalArticle

Eguchi, Hidetoshi ; Iwaki, Kentaro ; Shibata, Kohei ; Ogawa, Tadashi ; Ohta, Masayuki ; Kitano, Seigo. / Protease-activated receptor-2 regulates cyclooxygenase-2 expression in human bile duct cancer via the pathways of mitogen-activated protein kinases and nuclear factor kappa B. In: Journal of Hepato-Biliary-Pancreatic Sciences. 2011 ; Vol. 18, No. 2. pp. 147-153.
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abstract = "Background/purpose: Recent studies have suggested that protease-activated receptor-2 (PAR-2) activity correlates with cell proliferation and tumor growth, and its activation induces expression of cyclooxygenase-2 (COX-2). However, no previous reports have investigated PAR-2 signaling pathways in bile duct cancer. The aim of this study was to determine whether PAR-2 activation can regulate COX-2 expression via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) in human bile duct cancer cells. Methods: We immunohistochemically examined PAR-2 and COX-2 expression in 104 resected human specimens of extrahepatic bile duct cancer. We then determined how inhibitors of MAPKs and NF-κB signaling pathways influence COX-2 expression under PAR-2 activation in HuCCT1 and TKKK, human bile duct cancer cell lines. Results: PAR-2 and COX-2 proteins were immunohistochemically recognized in 63 and 57{\%} of specimens and were significantly correlated. PAR-2 agonist peptide activated mRNA and protein expression of COX-2 in HuCCT1 and TKKK. Pharmacologic blockade of p44/42 or p38 MAPK significantly inhibited PAR-2-activated mRNA and protein expression of COX-2 in both cells. COX-2 protein expression was also inhibited by the blocker of NF-κB pathway in both cells. Conclusions: PAR-2 may regulate COX-2 expression in human bile duct cancer via the MAPKs and NF-κB pathways.",
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AU - Ogawa, Tadashi

AU - Ohta, Masayuki

AU - Kitano, Seigo

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