Downloads: 177

Files in This Item:
File Description SizeFormat 
10.1111_cas.13431.pdf996.22 kBAdobe PDFView/Open
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKawata, Takahitoen
dc.contributor.authorTada, Koheien
dc.contributor.authorKobayashi, Masayukien
dc.contributor.authorSakamoto, Takashien
dc.contributor.authorTakiuchi, Yokoen
dc.contributor.authorIwai, Fumieen
dc.contributor.authorSakurada, Makien
dc.contributor.authorHishizawa, Masakatsuen
dc.contributor.authorShirakawa, Kotaroen
dc.contributor.authorShindo, Keisukeen
dc.contributor.authorSato, Hironorien
dc.contributor.authorTakaori-Kondo, Akifumien
dc.contributor.alternative菱澤, 方勝ja
dc.contributor.alternative白川, 康太郎ja
dc.contributor.alternative新堂, 啓祐ja
dc.contributor.alternative高折, 晃史ja
dc.date.accessioned2018-04-20T04:24:11Z-
dc.date.available2018-04-20T04:24:11Z-
dc.date.issued2018-01-
dc.identifier.issn1347-9032-
dc.identifier.urihttp://hdl.handle.net/2433/230782-
dc.description.abstractAdult T‐cell leukemia (ATL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated‐genome analysis has revealed mutations in many genes involved in the T‐cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL‐cell proliferation. We screened a siRNA library to examine signaling‐pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL‐cell proliferation. We therefore investigated the effect of mammalian target of rapamycin (mTOR) inhibitors, including the dual inhibitors PP242 and AZD8055 and the mTORC1 inhibitors rapamycin and everolimus, on human T‐cell leukemia virus type 1 (HTLV‐1)‐infected‐cell and ATL‐cell lines. Both dual inhibitors inhibited the proliferation of all tested cell lines by inducing G1‐phase cell‐cycle arrest and subsequent cell apoptosis, whereas the effects of the 2 mTORC1 inhibitors were limited, as they did not induce cell apoptosis. In the ATL‐cell lines and in the primary ATL samples, both dual inhibitors inhibited phosphorylation of AKT at serine‐473, a target of mTORC2, as well as that of S6K, whereas the mTORC1 inhibitors only inhibited mTORC1. Furthermore, AZD8055 more significantly inhibited the in vivo growth of the ATL‐cell xenografts than did everolimus. These results indicate that the PI3K/mTOR pathway is critical to ATL‐cell proliferation and might thus be a new therapeutic target in ATL.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherWiley-Blackwellen
dc.rights© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.en
dc.subjectadult T‐cell leukemiaen
dc.subjectAkten
dc.subjectHTLV-1en
dc.subjectmTORCen
dc.subjectmTORen
dc.titleDual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T-cell leukemiaen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleCancer Scienceen
dc.identifier.volume109-
dc.identifier.issue1-
dc.identifier.spage103-
dc.identifier.epage111-
dc.relation.doi10.1111/cas.13431-
dc.textversionpublisher-
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.addressPathogen Genomics Center, National Institute of Infectious Diseases, Tokyoen
dc.addressDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto Universityen
dc.identifier.pmid29077243-
dcterms.accessRightsopen access-
datacite.awardNumber16K09848-
jpcoar.funderName日本学術振興会ja
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
Appears in Collections:Journal Articles

Show simple item record

Export to RefWorks


Export Format: 


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.