title: Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemosensitivity in a human lung carcinoma cell line.
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.
authors.affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, 260-8670, Chiba, Japan.
authors.forename: Shigenari
authors.initials: S
authors.lastname: Omori
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Suda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanabe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Paige E
authors.initials: PE
authors.lastname: Pardington
authors.forename: Fanqing
authors.initials: F
authors.lastname: Chen
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D003114:Colony-Forming Units Assay; D004249:DNA Damage; D004265:DNA Helicases; D017931:DNA Primers; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D016373:DNA, Antisense / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D066298:In Vitro Techniques; D000072200:Ku Autoantigen; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays
chemical_list: D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D017931:DNA Primers; D016373:DNA, Antisense; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen