Diagnostic and therapeutic application of checkpoint gene T-fimbrin in gastrointestinal
| Project/Area Number |
16590609
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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 |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SASAKI Yasushi Sapporo Medical University, Cancer Research Inst., Dept Molecular Biology, Assistant Professor, 医学部, 講師 (70322328)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Kohzoh Sapporo Medical University, President, 学長 (60117603)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | T-fimbrin / DNA damage / DNA methylation / Cell Cycle Control / Chemosensitivity / Actin binding protein / Liver cancer |
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| Research Abstract |
Fimbrins (also known as plastins) are actin-binding proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. We previously reported that the upregulation of T-fimbrin, a fimbrin isoform, in association with G2 arrest following DNA damage and that a lack of T-fimbrin expression shortens the radiation-induced G2 arrest in Chinese hamster ovarian cells [Y.Sasaki et al. (2002) Int.J.Cancer, 97, 211-216]. In this study, we further investigated the role of T-fimbrin in DNA damage response using a panel of human liver cancer cell lines and small interfering RNA technology. T-fimbrin was differentially expressed in human liver cancer cell lines. Colony formation assays revealed that cell lines lacking T-fimbrin expression were highly sensitive to DNA damage compared to cell lines that express T-fimbrin. Using siRNA designed to target T-fimbrin, we demonstrated that silencing endogenous T-fimbrin causes a marked increase in the cellular sensitivity to VP-16 and UV irradiation. Moreover, T-fimbrin deletion abrogated UV-mediated cell cycle checkpoint, and consequently led to increased apoptotic cell death in resistant cells. These findings suggest that the status of T-fimbrin expression may be a useful molecular marker for predicting the responsiveness of cancer cells to treatment with chemotherapeutic drugs.
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Report
(3 results)
Research Products
(39 results)
