| Project/Area Number |
26462130
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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 |
Respiratory surgery
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAGAYASU Takeshi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686)
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| Co-Investigator(Kenkyū-buntansha) |
土谷 智史 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30437884)
日高 重和 長崎大学, 病院(医学系), 講師 (30380885)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 非小細胞肺癌 / Sp1 / DPD / EGFR / NSCLC / Gefitinib |
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| Outline of Final Research Achievements |
It has been shown that EGFR mutation status is associated with 5-FU sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR
mutation status and DPD, a 5-FU degrading enzyme, is unknown. In EGFR mutated cell, EGF treatment induced up-regulation of both Sp1 and DPD. EGFR-TKI and mithramycin A, a specific Sp-1 inhibitor, suppressed them. EGFR-TKI inhibited DPD protein expression only in EGFR-mutated cell lines. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line. The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status.
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