2012 Fiscal Year Final Research Report
Identification of genetic alterations in malignant mesothelioma and the development of new molecular diagnostic tools
Project/Area Number |
22300338
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Tumor diagnosis
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Research Institution | Aichi Cancer Center Research Institute |
Principal Investigator |
SEKIDO Yoshitaka 愛知県がんセンター(研究所), 分子腫瘍学部, 部長 (00311712)
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Project Period (FY) |
2010 – 2012
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Keywords | 中皮腫 / がん抑制遺伝子 / がん遺伝子 / ゲノム異常 / シグナル伝達 |
Research Abstract |
We identified that the LATS2 gene is a novel tumor suppressor gene of malignant mesothelioma (MM) and that LATS2 is inactivated in around 20% of MM cases. Inactivation of NF2 and/or LATS2 results in dysregulation of the Hippo tumor suppressive signaling cascade in MM cells. We found that Hippo pathway inactivation causes YAP activation and enhances transcription of the cyclin D and CTGF genes, which induces a more malignant phenotype of MM.
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[Journal Article] Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells.2012
Author(s)
Horio M, Sato M, Takeyama Y, Elshazley M, Yamashita R, Hase T, Yoshida K, Usami N, Yokoi K, Sekido Y, Kondo M, Toyokuni S, Gazdar AF, Minna JD, Hasegawa Y
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Journal Title
Ann Surg Oncol
Volume: 19 Supple3
Pages: S634-45
DOI
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[Journal Article] YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle promoting genes.2012
Author(s)
Mizuno T, Murakami H, Fujii M, Ishiguro F, Tanaka I, Kondo Y, Akatsuka S, Toyokuni S, Yokoi K, Osada H, Sekido Y
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Journal Title
Oncogene
Volume: 31
Pages: 5117-22
DOI
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[Journal Article] TGF-beta synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.2012
Author(s)
Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H, Sekido Y
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Journal Title
J Exp Med
Volume: 209
Pages: 479-94
DOI
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[Journal Article] The circadian clock gene BMAL1 is a novel therapeutic target for malignant mesothelioma.2012
Author(s)
Elshazley M, Sato M, Hase T, Yamashita R, Yoshida K, Toyokuni S, Ishiguro F, Osada H, Sekido Y, Yokoi K, Usami N, Shames DS, Kondo M, Gazdar AF, Minna JD, Hasegawa Y
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Journal Title
Int J Cancer
Volume: 131
Pages: 2820-31
DOI
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[Journal Article] Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.2012
Author(s)
Liu Y, Izumiya M, Abe K, Ochiai M, Jiang L, Nagai H, Okazaki Y, Murakami H, Sekido Y, Arai E, Kanai Y, Hino O, Takahashi T, Nakagama H, Toyokuni S
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Journal Title
PLoS One
Volume: 7
Pages: e43403
DOI
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[Journal Article] LATS2 is a tumor suppressor gene of malignant mesothelioma.2011
Author(s)
Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, Toyokuni S, Osada H, Sekido Y
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Journal Title
Cancer Res
Volume: 71
Pages: 873-83
DOI
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[Journal Article] 5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor.2011
Author(s)
Ali AH, Takizawa H, Kondo K, Matsuoka H, Toba H, Nakagawa Y, Kenzaki K, Sakiyama S, Kakiuchi S, Sekido Y, Sone S, Tangoku A
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Journal Title
Lung Cancer
Volume: 74
Pages: 48-54
DOI
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[Journal Article] Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells.2010
Author(s)
Tajima K, Ohashi R, Sekido Y, Hida T, Nara T, Hashimoto M, Iwakami S, Minakata K, Yae T, Takahashi F, Saya H, Takahashi K
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Journal Title
Oncogene
Volume: 29
Pages: 1941-51
DOI
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[Presentation] Inactivation of LATS2 indicates frequent dysregulation of the Merlin-Hippo signaling pathway in malignant mesothelioma.2010
Author(s)
Sekido Y, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, Toyokuni S, Osada H, Murakami H.
Organizer
10th International Conference of International Mesothelioma Interest Group (iMig)
Place of Presentation
京都国際会館(京都)
Year and Date
2010-09-02
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