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dc.contributor.authorHatta, Mamikoja
dc.contributor.authorMatsuzaki, Tomokoja
dc.contributor.authorMorioka, Yokoja
dc.contributor.authorYoshida, Yokoja
dc.contributor.authorNoda, Makotoja
dc.contributor.alternative野田, 亮ja
dc.contributor.alternative八田, 真美子ja
dc.date.accessioned2010-10-18T03:01:16Z-
dc.date.available2010-10-18T03:01:16Z-
dc.date.issued2009-12ja
dc.identifier.issn0898-6568ja
dc.identifier.urihttp://hdl.handle.net/2433/128757-
dc.description.abstractReck is a membrane-anchored glycoprotein identified as a transformation suppressor. Accumulating evidence indicates that Reck negatively regulates a wide spectrum of matrix metalloproteinases and is commonly down-regulated in a variety of malignant solid tumors. Physiological cues that regulate Reck expression, however, remained unknown. In this study, we found that Reck expression was up-regulated at high cell density, low serum, or after treatment with some kinase inhibitors, such as PP2 (Src inhibitor), LY294002 (PI3-kinase inhibitor), and PF573228 (FAK inhibitor), in mouse embryo fibroblasts. Curve fitting indicated that the levels of Reck protein and Reck mRNA are quadratic in the cell density. Other factors, including serum, extracellular matrix components (type I collagen and fibronectin), the kinase inhibitors, and some of their oncogenic targets (v-Src and PIK3CA mutants), modify the shape of the quadratic curve. Comparison of these modifications implicated Src in Reck down-regulation under sparse conditions, PI3-kinase in serum-induced Reck down-regulation, and FAK in Reck down-regulation at high cell density. Fibronectin and type I collagen down-regulated Reck, supporting the role of integrin-FAK signaling in Reck down-regulation at high cell density. Our study has revealed multiple signaling pathways impinging on Reck in cultured mouse embryo fibroblasts and sets a foundation for future studies to find effective Reck inducers of potential value in cancer therapy.ja
dc.format.mimetypeapplication/pdfja
dc.language.isoengja
dc.publisherElsevierja
dc.rights© 2009 Elsevier B.V.ja
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。This is not the published version. Please cite only the published version.ja
dc.subjectMmp2ja
dc.subjectFibroblastsja
dc.subjectSrcja
dc.subjectPI3Kja
dc.subjectCollagenja
dc.subjectFibronectinja
dc.subject.mesh1-Phosphatidylinositol 3-Kinase/antagonists & inhibitorsja
dc.subject.meshAnimalsja
dc.subject.meshCell Countja
dc.subject.meshChromones/pharmacologyja
dc.subject.meshEmbryo, Mammalian/cytologyja
dc.subject.meshExtracellular Matrix/metabolismja
dc.subject.meshFibroblasts/metabolismja
dc.subject.meshFocal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitorsja
dc.subject.meshMembrane Glycoproteins/geneticsja
dc.subject.meshMembrane Glycoproteins/metabolismja
dc.subject.meshMiceja
dc.subject.meshMorpholines/pharmacologyja
dc.subject.meshNIH 3T3 Cellsja
dc.subject.meshPyrimidines/pharmacologyja
dc.subject.meshQuinolones/pharmacologyja
dc.subject.meshSerum/metabolismja
dc.subject.meshSulfones/pharmacologyja
dc.subject.meshUp-Regulationja
dc.subject.meshsrc-Family Kinases/antagonists & inhibitorsja
dc.titleDensity- and serum-dependent regulation of the Reck tumor suppressor in mouse embryo fibroblasts.ja
dc.type.niitypeJournal Articleja
dc.identifier.ncidAA10671314ja
dc.identifier.jtitleCellular signallingja
dc.identifier.volume21ja
dc.identifier.issue12ja
dc.identifier.spage1885ja
dc.identifier.epage1893ja
dc.relation.doi10.1016/j.cellsig.2009.08.005ja
dc.textversionauthorja
dc.identifier.pmid19720143ja
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