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dc.contributor.authorNishizawa, Kojien
dc.contributor.authorNishiyama, Hiroyukien
dc.contributor.authorMatsui, Yoshiyukien
dc.contributor.authorKobayashi, Takashien
dc.contributor.authorSaito, Ryoichien
dc.contributor.authorKotani, Hirokazuen
dc.contributor.authorMasutani, Hiroshien
dc.contributor.authorOishi, Shinyaen
dc.contributor.authorToda, Yoshinobuen
dc.contributor.authorFujii, Nobutakaen
dc.contributor.authorYodoi, Junjien
dc.contributor.authorOgawa, Osamuen
dc.contributor.alternative松井, 喜之ja
dc.contributor.alternative小川, 修ja
dc.date.accessioned2012-07-23T01:34:27Z-
dc.date.available2012-07-23T01:34:27Z-
dc.date.issued2011-07-18-
dc.identifier.issn0143-3334-
dc.identifier.urihttp://hdl.handle.net/2433/158366-
dc.description.abstractThioredoxin-interacting protein (TXNIP), which has a tumor-suppressive function, is underexpressed in some human cancers. The function of TXNIP in vivo in carcinogenesis is not fully understood. Here, we show TXNIP to be downregulated in human bladder cancer according to grade and stage and also that loss of TXNIP expression facilitates bladder carcinogenesis using a mouse bladder cancer model. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer was found in 100% of Txnip knockout (KO) mice at week 8 of 0.025% BBN administration but in only 22% of wild-type (WT) mice at the same point. Among growth stimulators, phospho-extracellular signal-regulated kinase (pERK) expression was stronger during bladder carcinogenesis in Txnip-KO mice than in WT mice. We then evaluated TXNIP's effects on ERK activation through various growth stimulators and their receptors. Overexpression of TXNIP in human bladder cancer cells attenuated pERK expression upon stimulation with stromal cell-derived factor-1 (SDF-1) but not with epidermal growth factor or insulin-like growth factor-1. In Txnip-KO mice, immunohistochemical analysis showed enhanced expression of C-X-C chemokine receptor type 4 (CXCR4), the receptor of SDF-1, and of pERK in urothelial cells during BBN-induced bladder carcinogenesis. Finally, subcutaneous injection of CXCR4 antagonist, TF14016, attenuated pERK in urothelial cells and suppressed bladder carcinogenesis. These data indicate that TXNIP negatively regulates bladder carcinogenesis by attenuating SDF-1-CXCR4-induced ERK activation. This signal transduction pathway can be a potent target in preventing or treating bladder cancer.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherOxford University Pressen
dc.rights© The Author 2011. Published by Oxford University Press.en
dc.rightsThis is not the published version. Please cite only the published version.en
dc.rightsこの論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。ja
dc.subject.meshAgeden
dc.subject.meshAnimalsen
dc.subject.meshBlotting, Westernen
dc.subject.meshButylhydroxybutylnitrosamine/toxicityen
dc.subject.meshCarrier Proteins/geneticsen
dc.subject.meshCarrier Proteins/metabolismen
dc.subject.meshCarrier Proteins/physiologyen
dc.subject.meshChemokine CXCL12/geneticsen
dc.subject.meshChemokine CXCL12/metabolismen
dc.subject.meshDisease Models, Animalen
dc.subject.meshExtracellular Signal-Regulated MAP Kinases/geneticsen
dc.subject.meshExtracellular Signal-Regulated MAP Kinases/metabolismen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshImmunoenzyme Techniquesen
dc.subject.meshMaleen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshNeoplasm Stagingen
dc.subject.meshPrognosisen
dc.subject.meshRNA, Messenger/geneticsen
dc.subject.meshReceptors, CXCR4/antagonists & inhibitorsen
dc.subject.meshReceptors, CXCR4/geneticsen
dc.subject.meshReceptors, CXCR4/metabolismen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshSignal Transductionen
dc.subject.meshSurvival Rateen
dc.subject.meshThioredoxins/metabolismen
dc.subject.meshThioredoxins/physiologyen
dc.subject.meshUrinary Bladder Neoplasms/chemically induceden
dc.subject.meshUrinary Bladder Neoplasms/metabolismen
dc.subject.meshUrinary Bladder Neoplasms/pathologyen
dc.titleThioredoxin-interacting protein suppresses bladder carcinogenesis.en
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.ncidAA12072343-
dc.identifier.jtitleCarcinogenesisen
dc.identifier.volume32-
dc.identifier.issue10-
dc.identifier.spage1459-
dc.identifier.epage1466-
dc.relation.doi10.1093/carcin/bgr137-
dc.textversionauthor-
dc.identifier.pmid21771725-
dcterms.accessRightsopen access-
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