2014 Fiscal Year Final Research Report
Investigation of JAK/STAT signalling and development of new reagents regulating JAK/STAT pathways
| Project/Area Number |
24590091
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAGO Megumi 慶應義塾大学, 薬学部, 准教授 (30445192)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | JAK/STATシグナル系 / JAK2 変異体 / c-Myc活性化 / オルニチンデカルボキシラーゼ / 抗がん剤耐性 / ファンコニタンパク質 / フラーレン誘導体 |
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| Outline of Final Research Achievements |
JAK2/STAT pathway is involved in many cytokine signaling of which mechanism still requires precise investigation. JAK2 V617F mutation is observed in majority of patients with myeloproliferative neoplasms (MPNs). We investigated how JAK2V617F mutation induces dysregulated proliferation and tumorigenesis. JAK2 V617F mutation induced significant c-Myc mRNA expression mediated by STAT5 activation, which induced subsequent ornithine decarboxylase (ODC). An ODC inhibitor prevented proliferation of JAK2V617F cells. Further, JAK2V617F exhibited resistance to anti-cancer drugs such as CDDP. We found that FANCC, a member of the Fanconi anemia (FA) proteins, is responsible to the resistance against the drug-induced DNA damage. In addition, pyrrolidinium fullerene markedly induced apoptosis of JAK2 V617F cells. These observations indicated that fullerene derivatives are suitable candidates inhibiting the JAK2 V617F-mediated proliferation and tumorigenesis.
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| Free Research Field |
免疫学、生化学
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