| Project/Area Number |
14570540
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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 |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
TAKIGUCHI Yuichi Chiba University, University Hospital, Lecturer, 医学部附属病院, 講師 (30272321)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSU Katsushi Chiba University, Graduate School of Medicine, Assistant (20291106)
TATSUMI Koichiro Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10207061)
KURIYAMA Takayuki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20009723)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | DNA repair gene / Ku70 / antisense oligonucleotide / radiosensitivity / chemosensitivity / gene therapy / lung cancer |
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| Research Abstract |
Ku70 protein, cooperating with Ku80 and DNA-dependent protein kinase (DNA-PK) catalytic subunits (DNA-PKcs), is involved in DNA double-strand break (DNA DSB) repair and V(D)J recombination. Recent studies have revealed increased ionizing radiosensitivity in Ku70-deficient cells. The presented study, using a human squamous cell lung carcinoma cell line, demonstrated that introduction of an antisense Ku70 nucleic acid made the cells more radio-and chemosensitive than the parental cells. Ku70 protein expression was suppressed in the cells with antisense Ku70 construct when compared to the wild type cells : A relatively small but statistically significant increase in radiosensitivity of the cells was achieved by the introduction of the antisense Ku70. The increased radiosensitivity in vitro was accompanied by an approximately two-fold increase in a and alb values in a linear-quadratic model. The antisense Ku70 increased the chemosensitivity of the cells to some DNA-damaging agents such as bleomycin and methyl methanesulfonate, but not to cisplatin, mitomycin C, and paclitaxel. This system provides us with partial suppression of Ku70, and will be a useful experimental model for investigating the physiological roles of the DNA DSB repair gene.
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