2005 Fiscal Year Final Research Report Summary
Diagnostic and therapeutic application of checkpoint gene CHFR in oral squamous cell cancer.
| Project/Area Number |
16390597
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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 |
Surgical dentistry
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TOKINO Takashi Sapporo Medical University, Cancer Research Inst, Dept Molecular Biology, Professor, 医学部, 教授 (40202197)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATSUKA Hiroyoshi Sapporo Medical University, Professor, 医学部, 教授 (50165180)
KIDO Sachie Sapporo Medical University, Instructor, 医学部, 助手 (20363690)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Cancer / Translational Research / Chemosensitivity / Cell Cycle Control / Ubiquitin ligase / ユビキチンリガーゼ |
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| Research Abstract |
Alterations in the function of cell cycle checkpoints are frequently detected in oral squamous cell carcinomas (OSCCs), and are often associated with the sensitivity of the cancer cells to chemotherapeutic drugs. Recently, a mitotic checkpoint gene, Chfr, was shown to be inactivated by promoter methylation and point mutations in various human tumors. Here we show that the absence of its product, CHFR, is associated with mitotic checkpoint dysfunction, and that cancer cells lacking CHFR are sensitive to microtubule inhibitors. Checkpoint impairment appears to be caused by a prophase defect in this case, as OSCC cells lacking CHFR showed phosphorylation of histone H3 on Ser10 and translocation of cyclin B1 to the nucleus. When CHFR-deficient OSCC cells were treated with a microtubule inhibitor (docetaxel or paclitaxel), significant numbers of apoptotic cells were observed. Moreover, disruption of CHFR using small interfering RNA (siRNA) impaired the mitotic checkpoint, thereby reducing the ability of OSCC cells to arrest at G2/M phase and making them more sensitive to microtubule inhibitors. Our results suggest that CHFR could be a useful molecular target for chemotherapy.
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Research Products
(50 results)
