Cited 18 times in
Peroxisome proliferator-activated receptor ligand MCC-555 suppresses intestinal polyps in ApcMin/+ mice via extracellular signal-regulated kinase and peroxisome proliferator-activated receptor-dependent pathways
DC Field | Value | Language |
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dc.contributor.author | 윤주헌 | - |
dc.date.accessioned | 2015-05-19T17:10:09Z | - |
dc.date.available | 2015-05-19T17:10:09Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/107632 | - |
dc.description.abstract | A large body of studies has suggested that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, such as thiazolidinedione, are potent candidates for chemopreventive agents. MCC-555 is a PPARgamma/alpha dual agonist and has been shown previously to induce apoptosis in vitro; however, the molecular mechanisms by which MCC-555 affects antitumorigenesis in vivo are poorly understood. In this study, we explored the antitumorigenic effects of MCC-555 both in cell culture and in Apc-deficient mice, an animal model for human familial adenomatous polyposis. MCC-555 increased MUC2 expression in colorectal and lung cancer cells, and treatment with the PPARgamma antagonist GW9662 revealed that MUC2 induction by MCC-555 was mediated in a PPARgamma-dependent manner. Moreover, MCC-555 increased transcriptional activity of human and mouse MUC2 promoters. Subsequently, treatment with MCC-555 (30 mg/kg/d) for 4 weeks reduced the number of small intestinal polyps to 54.8% of that in control mice. In agreement with in vitro studies, enhanced Muc2 expression was observed in the small intestinal tumors of Min mice treated with MCC-555, suggesting that MUC2 expression may be associated at least in part with the antitumorigenic action of MCC-555. In addition, highly phosphorylated extracellular signal-regulated kinase (ERK) was found in the intestinal tumors of MCC-555-treated Min mice, and inhibition of the ERK pathway by a specific inhibitor markedly suppressed MCC-555-induced Muc2 expression in vitro. Overall, these results indicate that MCC-555 has a potent tumor suppressor activity in intestinal tumorigenesis, likely involving MUC2 up-regulation by ERK and PPARgamma pathways | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 2779~2787 | - |
dc.relation.isPartOf | MOLECULAR CANCER THERAPEUTICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adenomatous Polyposis Coli Protein/deficiency* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Colorectal Neoplasms/enzymology | - |
dc.subject.MESH | Colorectal Neoplasms/genetics | - |
dc.subject.MESH | Colorectal Neoplasms/pathology | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/metabolism* | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic/drug effects | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Intestinal Polyps/enzymology* | - |
dc.subject.MESH | Intestinal Polyps/pathology* | - |
dc.subject.MESH | Ligands | - |
dc.subject.MESH | Lung Neoplasms/genetics | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mucin-2 | - |
dc.subject.MESH | Mucins/genetics | - |
dc.subject.MESH | Mucins/metabolism | - |
dc.subject.MESH | Peroxisome Proliferator-Activated Receptors/metabolism* | - |
dc.subject.MESH | RNA, Messenger/genetics | - |
dc.subject.MESH | RNA, Messenger/metabolism | - |
dc.subject.MESH | Thiazolidinediones/chemistry | - |
dc.subject.MESH | Thiazolidinediones/pharmacology* | - |
dc.subject.MESH | Transcription, Genetic/drug effects | - |
dc.title | Peroxisome proliferator-activated receptor ligand MCC-555 suppresses intestinal polyps in ApcMin/+ mice via extracellular signal-regulated kinase and peroxisome proliferator-activated receptor-dependent pathways | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Otorhinolaryngology (이비인후과학) | - |
dc.contributor.googleauthor | Kiyoshi Yamaguchi | - |
dc.contributor.googleauthor | Maria Cekanova | - |
dc.contributor.googleauthor | Michael F. McEntee | - |
dc.contributor.googleauthor | Joo-Heon Yoon | - |
dc.contributor.googleauthor | Susan M. Fischer | - |
dc.contributor.googleauthor | Ingrid B. Renes | - |
dc.contributor.googleauthor | Isabelle Van Seuningen | - |
dc.contributor.googleauthor | Seung Joon Ba다 | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-08-0173 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02604 | - |
dc.relation.journalcode | J02254 | - |
dc.identifier.eissn | 1538-8514 | - |
dc.identifier.pmid | 18790758 | - |
dc.subject.keyword | MCC-555 | - |
dc.subject.keyword | colorectal cancer | - |
dc.subject.keyword | ApcMin/+ mice | - |
dc.subject.keyword | MUC2 | - |
dc.subject.keyword | PPARs | - |
dc.subject.keyword | ERK pathway | - |
dc.contributor.alternativeName | Yoon, Joo Heon | - |
dc.contributor.affiliatedAuthor | Yoon, Joo Heon | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 7 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 2779 | - |
dc.citation.endPage | 2787 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER THERAPEUTICS, Vol.7(9) : 2779-2787, 2008 | - |
dc.identifier.rimsid | 54801 | - |
dc.type.rims | ART | - |
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