International Journal of Radiation Oncology * Biology * Physics
Volume 73, Issue 4 , Pages 976-979 , 15 March 2009

Major Vault Protein May Affect Nonhomologous End-Joining Repair and Apoptosis Through Ku70/80 and BAX Downregulation in Cervical Carcinoma Tumors

  • Marta Lloret, M.D., Ph.D.

      Affiliations

    • Radiation Oncology Department, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • Corresponding Author InformationReprint requests to: Marta Lloret, M.D., Ph.D., Radiation Oncology, Hospital Universitario Dr. Negrin, Barranco de la Ballena s/n, 35010, Las Palmas de Gran Canaria, Spain. Tel: (00) 34-92-845-0284; Fax: (00) 34-92-844-9127
    • ,
  • Pedro Carlos Lara, M.D., Ph.D.

      Affiliations

    • Radiation Oncology Department, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • ,
  • Elisa Bordón, Ph.D.

      Affiliations

    • Radiation Oncology Department, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • ,
  • Fausto Fontes, B. Pharm.

      Affiliations

    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • ,
  • Agustin Rey, M.D., Ph.D.

      Affiliations

    • Pathology Department, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • ,
  • Beatriz Pinar, M.D., Ph.D.

      Affiliations

    • Radiation Oncology Department, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • ,
  • Orlando Falcón, M.D., Ph.D.

      Affiliations

    • Instituto Canario de Investigación del Cáncer, Canary Islands, Spain
    • Gynecological Oncology Department, Hospital Universitario Materno-Infantil, Las Palmas de Gran Canaria, Spain

Received 16 November 2008 ,Accepted 18 November 2008.

References 

  1. Steiner E, Holzmann K, Elbling L, et al. Cellular functions of vaults and their involvement in multidrug resistance. Curr Drug Targets. 2006;8:923–934
  2. Silva P, West CM, Slevin N, et al. Tumor expression of major vault protein is an adverse prognostic factor for radiotherapy outcome in oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2007;69:133–140
  3. Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol. 2007;83:781–791
  4. Lloret M, Lara PC, Bordón E, et al. MVP expression is related to IGF1-R in cervical carcinoma patients treated by radiochemotherapy. Gynecol Oncol. 2008;110:304–307
  5. Bottke D, Koychev D, Busse A, et al. Fractionated irradiation can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines. Radiat Res. 2008;170:41–48
  6. Miwa M, Masutani M. PolyADP-ribosylation and cancer. Cancer Sci. 2007;98:1528–1535
  7. Salhab M, Jiang WG, Newbold RF, et al. The expression of gene transcripts of telomere-associated genes in human breast cancer: Correlation with clinico-pathological parameters and clinical outcome. Breast Cancer Res Treat. 2008;109:35–46
  8. Emre N, Raval-Fernandes S, Kickhoefer VA, et al. Analysis of MVP and VPARP promoters indicates a role for chromatin remodelling in the regulation of MVP. Biochim Biophys Acta. 2004;1678:33–46
  9. Hochegger H, Dejsuphong D, Fukushima T, et al. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. EMBO J. 2006;25:1305–1314
  10. Chang HJ, Jung KH, Kim DY. Regulation of the proapoptotic factor Bax by Ku70-dependent deubiquitylation. Proc Natl Acad Sci U S A. 2008;105:5117–5122
  11. Wang Q, Gao F, May WS, et al. Bcl2 negatively regulates DNA double-strand-break repair through a nonhomologous end-joining pathway. Mol Cell. 2008;29:488–498
  12. Toulany M, Kehlbach R, Florczak U, et al. Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Ther. 2008;7:1772–1781
  13. Cosaceanu D, Budiu RA, Carapancea M, et al. Ionizing radiation activates IGF-1R triggering a cytoprotective signalling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene. 2007;26:2423–2434
  14. Chen CS, Wang YC, Yang HC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation. Cancer Res. 2007;67:5318–5327
  15. Teoh NC, Dan YY, Swisshelm K, et al. Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology. 2008;47:2078–2088

 This work was subsidized by Fondo de Investigaciones Sanitarias Grants 1035/98 and 0855/01. E. Bordón and F. Fontes were supported by an educational grant from the Instituto Canario de Investigación del Cáncer.

 Conflict of interest: none.

PII: S0360-3016(08)03791-7

doi: 10.1016/j.ijrobp.2008.11.013

International Journal of Radiation Oncology * Biology * Physics
Volume 73, Issue 4 , Pages 976-979 , 15 March 2009

Article Tools

* Image Usage & Resolution