Study of the molecular mechanism of neural tumor formation mediatedby NF1 gene deficiency
| Project/Area Number | 22390281 |
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
ARAKI Norie 熊本大学, 大学院・生命科学研究部, 准教授 (80253722)
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| Co-Investigator(Kenkyū-buntansha) |
KURATSU Juniti 熊本大学, 大学院・命科学研究部, 教授 (20145296)
IRIE Atsushi 熊本大学, 大学院・命科学研究部, 講師 (30250343)
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| Co-Investigator(Renkei-kenkyūsha) |
SAYA Hideyuki 慶應義塾大学, 医学部, 教授 (80264282)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed(Fiscal Year 2012)
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| Budget Amount *help |
¥19,110,000 (Direct Cost : ¥14,700,000、Indirect Cost : ¥4,410,000)
Fiscal Year 2012 : ¥5,460,000 (Direct Cost : ¥4,200,000、Indirect Cost : ¥1,260,000)
Fiscal Year 2011 : ¥5,460,000 (Direct Cost : ¥4,200,000、Indirect Cost : ¥1,260,000)
Fiscal Year 2010 : ¥8,190,000 (Direct Cost : ¥6,300,000、Indirect Cost : ¥1,890,000)
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| Keywords | 神経線維腫症 / NF1 / プロテオミクス / 腫瘍抑制シグナル / Neurofibromin / NF2 / Merlin / siRNA |
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| Research Abstract |
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that predisposesindividuals to developing benign neurofibromas and malignant peripheral nerve sheathtumors (MPNSTs). The molecular mechanism of NF1-associated tumor pathogenesis has beenlargely unknown, and the strategy of medical treatments for NF1 tumors has not beenestablished. To identify the molecular marker/target in malignant tumors mediated by NF1gene deficiency, we established the NF1 gene knockdown (KD) system in neural cells asa NF1 disease model, and analyzed the expression profiles of genes/proteins by anintegrated proteomics. Of 4000 non-redundant proteins semi-quantitatively identified,we extracted 38 molecular signals which were abnormally upregulated in NF1 KD cellscompared with control cells. These proteins were mostly related to cell motility,apoptosis, and cell differentiation, and including several novel protein networks inneuronal cells, such as TCTP(Translationally Controlled Tumor Protein)-mTOR signal andDynein-GR-COX1 signal. We confirmed that these signals were significantly up-regulatedin NF1-deficient neural cells via the activation of MAPK/PI3K-AKT signaling in responseto growth factors. The knockdown or inhibitor treatments of these signals suppressed theviability and differentiation of NF1 disease model/tumor cells. These results suggestthat these novel NF1-related signals are functionally implicated in the tumorigenesisand it’s progression, and serves as a diagnostic biomarker/therapeutic target for NF1tumors.
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Report
(4results)
Research Products
(146results)
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Shibata T, Watari K, Izumi H, Kawahara A, Hattori S, Fukumitsu C, Murakami Y, Takahashi R, Toh U, Ito KI, Ohdo S, Tanaka M, Kage M, Kuwano M, Ono M.
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[Journal Article] Enhancement ofhuman cancer cell motility and invasivenessby anaphylatoxin C5a via aberrantlyexpressed C5a-receptor (CD88).2013
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[Journal Article] Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin alpha V.2013
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[Journal Article] Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a-receptor (CD88).2013
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Shibui S, Narita Y, Mizusawa J, Beppu T, Ogasawara K, Sawamura Y, Kobayashi H, Nishikawa R, Mishima K, Muragaki Y, Maruyama T, Kuratsu J, Nomura K etl .
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[Presentation] An integrated proteomics by iPEACH, anew application, identified novel activatedsignal cascades in chemotherapy resistantmalignant gliomas2012
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Araki N, Mizugushi S,Morikawa T , kawano S, Y amaguchi A,Kobayashi D, Hirayama M, Midorikawa U,Nakamura H, Kuratsu J
Organizer
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[Presentation] An integrated proteomics by iPEACH, a new application, identified novel activated signal cascades in chemotherapy resistant malignant gliomas2012
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[Presentation] Integrated Proteomics Identified Translationally Controlled Tumor Protein as a Biological Target for Neurofibroma and Malignant Peripheral Nerve Sheath Tumors2012
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Organizer
HUPO 11th Annual World Congress
Place of Presentation
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