| Project/Area Number |
17591973
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
ITO Mizue Tokyo Medical University, Medicine, VISITING LECTURER, 医学部, 客員講師 (00398760)
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| Co-Investigator(Kenkyū-buntansha) |
TAKADA Eiko Tokyo Medical University, Medicine, LECTURER, 医学部, 講師 (50110903)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | squamous cell carcinoma / drug resistance / apoptosis / TRAIL / JNK / 扁平上皮癌 / 薬剤耐性 / アポトーシス / MAPKs |
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| Research Abstract |
Chemotherapeutic agents have been used for treatment of patients with squamous cell carcinoma (SCC). However, their clinical use is limited by problems such as severe side effects and inherent and/or acquired resistance to these agents. Moreover, some forms of SCC cells tend to metastasize to near/distant regions such as lymph nodes. We have established several SCC lines from patients with primary (MIT) and/or metastatic (MIL) tumors. These cell lines were assessed by sensitivity to chemotherapeutic agents and TNF-related apoptosis-inducing ligand (TRAIL). The combined treatment of these agents resulted in an efficient killing of SCC cells. We and others have recently demonstrated that a sustained activation of JNK is involved in the induction of apoptosis following stimulation with chemotherapeutic agents. In this study, we examined whether TRAIL-induced apoptosis involves JNK activation in SCC cells. Cell lines from MIT tumor were sensitive to TRAIL, whereas those from MIL were resistant. JNK was phosphorylated in response to TRAIL in MIT, but not MIL cells, as assessed by Western blotting using antibodies specific for phospho-JNK. To address whether phosphorylation of JNK is required for TRAIL-induced cell death, MIT cells over-expressing dominant-negative form of JNK (dnJNK) were established. The dnJNK-expressing MIT cells became resistant to TRAIL, comparable to MIL cells. Thus, activation of JNK is necessary for TRAIL-induced apoptotic cell death in SCC cells.
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