International Journal of Radiation Oncology * Biology * Physics
Volume 77, Issue 3 , Pages 877-885 , 1 July 2010

Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

  • Muneyasu Urano, M.D., Ph.D.

      Affiliations

    • Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
    • Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY
    • Corresponding Author InformationReprint requests to: Muneyasu Urano, M.D., Ph.D., Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Tel: (646) 888-2153; Fax: (646) 422-0247
    • ,
  • Fuqiu He, Ph.D.

      Affiliations

    • Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
    • ,
  • Akiko Minami, MD.

      Affiliations

    • Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY
    • ,
  • C. Clifton Ling, Ph.D.

      Affiliations

    • Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY
    • ,
  • Gloria C. Li, Ph.D.

      Affiliations

    • Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY

Received 29 June 2009 ,Revised 23 December 2009 ,Accepted 28 December 2009.

References 

  1. Gullo C, Au M, Feng G, et al. The biology of Ku and its potential oncogenic role in cancer—Review. Biochim Biophys Acta. 2006;1765:223–234
  2. Velerie K, Povirk LF. Regulation and mechanisms of mammalian double-strand break repair. Oncogene. 2003;22:5792–5812
  3. Walker JR, Corpina RA, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature. 2001;412:607–614
  4. Tuteja R, Tuteja N. Ku autoantigen: A multifunctional DNA-binding protein. Crit Rev Biochem Mol Biol. 2000;35:1–33
  5. Wang J, Dong X, Myung K, et al. Identification of two domains of the p70 Ku protein mediating dimerization with p80 and DNA binding. J Biol Chem. 1998;273:842–848
  6. Kurimasa A, Ouyang H, Dong L-J, et al. Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis. Proc Natl Acad Sci USA. 1999;96:1403–1408
  7. Nussenzweig A, Chen C, da Costa Soares V, et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature. 1996;382:551–555
  8. Ouyang H, Nussenzweig A, Kurimasa A, et al. Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo. J Exp Med. 1997;186:921–929
  9. He F, Li L, Kim D, et al. Adenovirus-mediated expression of a dominant-negative Ku70 fragment radiosensitizes human tumor cells under aerobic and hypoxic conditions. Cancer Res. 2007;67:634–642
  10. Li GC, He F, Shao X, et al. Adenovirus-mediated heat-activated antisense Ku70 expression radiosensitizes tumor cells in vitro and in vivo. Cancer Res. 2003;63:3268–3274
  11. Urano M, Huang Y, He F, et al. Response to multiple radiation doses of fibroblasts over-expressing dominant-negative KU70. Int J Radiat Oncol Biol Phys. 2008;71:533–541
  12. Thames HD, Withers HR, Peters LJ, et al. Changes in early and late radiation responses with altered dose fractionation: Implications for dose-survival relationships. Int J Radiat Oncol Biol Phys. 1982;8:219–226
  13. Sah NK, Munshi A, Nishikawa T, et al. Adenovirus-mediated wild-type p53 radiosensitizes human tumor cells by suppressing DNA repair capacity. Mol Cancer Ther. 2003;2:1223–1231
  14. Spiro IJ, Kennedy KA, Stickler R, et al. Cellular and molecular repair of x-ray-induced damage: Dependence on oxygen tension and nutritional status. Radiat Res. 1985;101:144–155
  15. Rao BS, Hopwood LE. Effect of hypoxia on recovery from damage induced by heat and radiation in plateau-phase CHO cells. Radiat Res. 1985;101:312–325
  16. Urano M, He F, Minami A, et al. Hypoxia-induced lethal damage is enhanced by inhibiting the repair of DNA damage but reparable when reoxygenated. Presented at the 55th Annual Radiation Research Meeting, October 3-7, 2009, Savannah, GA p. 156.
  17. Lee SE, Pulaski CR, He DM, et al. Isolation of mammalian cell mutants that are X-ray sensitive, impaired in DNA double-strand break repair and defective for V(D)J recombination. Mutat Res. 1995;336:279–291
  18. Marangoni E, Foray N, O'Driscoll M, et al. A Ku80 fragment with dominant-negative activity imparts a radiosensitive phenotype to CHO-K1 cells. Nucleic Acids Res. 2000;28:4778–4782
  19. Nussenzweig A, Sokol K, Burgman P, et al. Hypersensitivity of Ku80-deficient cell lines and mice to DNA damage. Proc Natl Acad Sci USA. 1997;94:13588–13593
  20. Okayasu R, Okada M, Okabe A, et al. Repair of DNA damage induced by accelerated heavy ions in mammalian cells proficient and deficient in the non-homologous end-joining pathway. Radiat Res. 2006;165:59–67
  21. Ross GM, Eady JJ, Mithal NP, et al. DNA strand break rejoining defect in xrs-6i Is complemented by transfection with the human Ku80 gene1. Cancer Res. 1995;55:1235–1238
  22. Schulte-Uentrop L, El-Awady RA, Schliecker L, et al. Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease and ionizing radiation-induced DNA double-strand breaks. Nucleic Acids Res. 2008;36:2561–2569
  23. Singleton BK, Priestley A, Steingrimsdottir H, et al. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol. 1997;17:1264–1273
  24. Wang H, Wang X, Zhang P, Wang Y. The Ku-dependent non-homologous end-joining but not other repair pathway is inhibited by high linear energy transfer ionizing radiation. DNA Repair. 2008;7:725–733
  25. Errami A, Smider V, Rathmell WK, et al. Ku86 defines the genetic defect and restores X-ray resistance and V(D)J recombination to complementation group 5 hamster cell mutants. Mol Cell Biol. 1996;16:1519–1526
  26. Smider V, Rathmell WK, Lieber MR, et al. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science. 1994;266:288–291
  27. Taccioli GE, Gottlieb TM, Blunt T, et al. Ku80: Product of the XRCC5 and its role in DNA repair and V(D)J recombination. Science. 1994;265:1442–1445
  28. Adachi N, Ishino T, Ishii Y, et al. DNA ligase IV-deficient cells are more resistant to ionizing radiation in the absence of Ku70. Proc Natl Acad Sci USA. 2001;98:12109–12113
  29. Gu Y, Jin S, Gao Y, et al. Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination. Proc Natl Acad Sci USA. 1997;94:8076–8081
  30. Utsumi H, Tano K, Takata M, et al. Requirement for repair of DNA double-strand breaks by homologous recombination in split-dose recovery. Radiat Res. 2001;155:680–686
  31. Belenkov AL, Paiement J-P, Panasci LC, et al. An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Cancer Res. 2002;62:5888–5896
  32. Marangoni E, LeRomancer M, Foray N, et al. Transfer of Ku86 antisense decreases the radioresistance of human fibroblasts. Cancer Gene Ther. 2000;7:339–346
  33. Omori S, Takiguchi U, Suda A, et al. Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and chemo-sensitivity in a human lung carcinoma cell line. DNA Repair. 2002;1:299–310
  34. Ayene IS, Ford LP, Koch CJ. Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and γ radiation. Mol Cancer Ther. 2005;4:529–536
  35. Nimura Y, Kawata T, Uzawa K, et al. Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo. Int J Oncol. 2007;30:1477–1484
  36. Negroni A, Strolnati L, Grollino MG, et al. Radioresistance in a tumour cell line correlates with radiation inducible Ku70/80 end-binding activity. Int J Radiat Biol. 2008;84:265–276

 Supported by National Institutes of Health-National Cancer Institute Grants CA56909, CA109772, and P01 CA115675.

 Conflict of interest: none.

PII: S0360-3016(10)00012-X

doi: 10.1016/j.ijrobp.2009.12.062

International Journal of Radiation Oncology * Biology * Physics
Volume 77, Issue 3 , Pages 877-885 , 1 July 2010

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