| RRC ID |
41761
|
| 著者 |
Omori S, Takiguchi Y, Suda A, Sugimoto T, Miyazawa H, Takiguchi Y, Tanabe N, Tatsumi K, Kimura H, Pardington PE, Chen F, Chen DJ, Kuriyama T.
|
| タイトル |
Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemosensitivity in a human lung carcinoma cell line.
|
| ジャーナル |
DNA Repair (Amst)
|
| Abstract |
Ku70 protein, cooperating with Ku80 and DNA-dependent protein kinase (DNA-PK) catalytic subunit (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 alpha and alpha/beta 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.
|
| 巻・号 |
1(4)
|
| ページ |
299-310
|
| 公開日 |
2002-4-29
|
| DOI |
10.1016/s1568-7864(02)00006-x
|
| PII |
S156878640200006X
|
| PMID |
12509248
|
| MeSH |
Antigens, Nuclear / genetics
Antineoplastic Agents / therapeutic use
Blotting, Northern
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / radiotherapy*
Colony-Forming Units Assay
DNA Damage
DNA Helicases*
DNA Primers
DNA Repair / drug effects*
DNA Repair / genetics
DNA, Antisense / pharmacology
DNA, Neoplasm / drug effects
DNA-Binding Proteins / antagonists & inhibitors*
DNA-Binding Proteins / genetics
Electrophoretic Mobility Shift Assay
Humans
In Vitro Techniques
Ku Autoantigen
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / radiotherapy*
Transfection
Tumor Cells, Cultured / drug effects
Tumor Cells, Cultured / radiation effects
X-Rays
|
| IF |
3.339
|
| 引用数 |
63
|
|
WOS 分野
|
TOXICOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
|
