| 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. | |
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MedLine Citation:
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PMID: 20740367 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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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Authors:
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Hidetoshi Eguchi; Kentaro Iwaki; Kohei Shibata; Tadashi Ogawa; Masayuki Ohta; Seigo Kitano |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of hepato-biliary-pancreatic sciences Volume: 18 ISSN: 1868-6982 ISO Abbreviation: J Hepatobiliary Pancreat Sci Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101528587 Medline TA: J Hepatobiliary Pancreat Sci Country: Japan |
Other Details:
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Languages: eng Pagination: 147-53 Citation Subset: IM |
Affiliation:
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Department of Surgery I, Oita University Faculty of Medicine, 1-1 Hasama-machi, Yufu, Oita, 879-5593, Japan, heguchi@med.oita-u.ac.jp. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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