Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemosensitivity in a human lung carcinoma cell line

Shigenari Omori, Yuichi Takiguchi, Akira Suda, Takaaki Sugimoto, Hiroshi Miyazawa, Yasuo Takiguchi, Nobuhiro Tanabe, Koichiro Tatsumi, Hiroshi Kimura, Paige E. Pardington, Fanqing Chen, David J. Chen, Takayuki Kuriyama

Research output: Contribution to journalArticle

66 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalDNA repair
Volume1
Issue number4
DOIs
StatePublished - Apr 29 2002

Keywords

  • Antisense nucleic acid
  • DNA double-strand break repair
  • DNA repair
  • Ionizing radiation
  • Ku70

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Omori, S., Takiguchi, Y., Suda, A., Sugimoto, T., Miyazawa, H., Takiguchi, Y., Tanabe, N., Tatsumi, K., Kimura, H., Pardington, P. E., Chen, F., Chen, D. J., & Kuriyama, T. (2002). Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemosensitivity in a human lung carcinoma cell line. DNA repair, 1(4), 299-310. https://doi.org/10.1016/S1568-7864(02)00006-X