TY - JOUR
T1 - Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemosensitivity in a human lung carcinoma cell line
AU - Omori, Shigenari
AU - Takiguchi, Yuichi
AU - Suda, Akira
AU - Sugimoto, Takaaki
AU - Miyazawa, Hiroshi
AU - Takiguchi, Yasuo
AU - Tanabe, Nobuhiro
AU - Tatsumi, Koichiro
AU - Kimura, Hiroshi
AU - Pardington, Paige E.
AU - Chen, Fanqing
AU - Chen, David J.
AU - Kuriyama, Takayuki
N1 - Funding Information:
We thank Professor Jun-ichi Miyazaki (Department of Nutrition and Physiological Chemistry, Osaka University Medical School) for the kind gift of the mammalian expression vector pCAGGS, Nippon Kayaku K. K. Tokyo, Japan for the gift of bleomycin, Kyowa Hakko Kogyo K. K., Tokyo, Japan for the gift of mitomycin C, and the Japan branch of Bristol-Myers Squibb K. K. for the gift of cisplatin and paclitaxel. The technical assistance of Reiko Kunii, and the secretarial assistance of Chieko Handa-Miyagi (Department of Respirology, Graduate School of Medicine, Chiba University) are also much appreciated. This work was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2002/4/29
Y1 - 2002/4/29
N2 - 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 α and α/β 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.
AB - 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 α and α/β 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.
KW - Antisense nucleic acid
KW - DNA double-strand break repair
KW - DNA repair
KW - Ionizing radiation
KW - Ku70
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U2 - 10.1016/S1568-7864(02)00006-X
DO - 10.1016/S1568-7864(02)00006-X
M3 - Article
C2 - 12509248
AN - SCOPUS:0037193539
SN - 1568-7864
VL - 1
SP - 299
EP - 310
JO - DNA repair
JF - DNA repair
IS - 4
ER -