| The role of PGE(2)-associated inflammatory responses in gastric cancer development. | |
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MedLine Citation:
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PMID: 23053397 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Accumulating evidence indicates that inflammation plays a critical role in cancer development. Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme for prostanoid biosynthesis, including prostaglandin E(2) (PGE(2)), and plays a key role in both inflammation and cancer. It has been demonstrated that inhibition of COX-2 and PGE(2) receptor signaling results in the suppression of tumor development in a variety of animal models. However, the molecular mechanisms underlying COX-2/PGE(2)-associated inflammation in carcinogenesis have not yet been fully elucidated. In order to study the role of PGE(2)-associated inflammatory responses in tumorigenesis, it is important to use in vivo mouse models that recapitulate human cancer development from molecular mechanisms with construction of tumor microenvironment. We have developed a gastritis model (K19-C2mE mice) in which an inflammatory microenvironment is constructed in the stomach via induction of the COX-2/PGE(2) pathway. We also developed a gastric cancer mouse model (Gan mice) in which the mice develop inflammation-associated gastric tumors via activation of both the COX-2/PGE(2) pathway and Wnt signaling. Expression analyses using these in vivo models have revealed novel mechanisms of the inflammatory responses underlying gastric cancer development. PGE(2)-associated inflammatory responses activate epidermal growth factor receptor (EGFR) signaling through the induction of EGFR ligands and ADAMs that release EGFR ligands from the cell membrane. In Gan mice, a combination treatment with EGFR and COX-2 inhibitors significantly suppresses gastric tumorigenesis. Moreover, PGE(2)-associated inflammation downregulates tumor suppressor microRNA, miR-7, in gastric cancer cells, which suppresses epithelial differentiation. These results indicate that PGE(2)-associated inflammatory responses promote in vivo gastric tumorigenesis via several different molecular mechanisms. |
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Authors:
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Hiroko Oshima; Masanobu Oshima |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-11 |
Journal Detail:
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Title: Seminars in immunopathology Volume: - ISSN: 1863-2300 ISO Abbreviation: Semin Immunopathol Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101308769 Medline TA: Semin Immunopathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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