International Journal of Radiation Oncology * Biology * Physics
Volume 77, Issue 2 , Pages 566-574 , 1 June 2010

Depletion of Securin Induces Senescence After Irradiation and Enhances Radiosensitivity in Human Cancer Cells Regardless of Functional p53 Expression

  • Wen-Shu Chen

      Affiliations

    • Department of Life Science, Tzu Chi University, Hualien, Taiwan
  • ,
  • Yi-Chu Yu

      Affiliations

    • Department of Life Science, Tzu Chi University, Hualien, Taiwan
  • ,
  • Yi-Jang Lee, Ph.D.

      Affiliations

    • Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
  • ,
  • Ji-Hshiung Chen, Ph.D.

      Affiliations

    • Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
  • ,
  • Hsue-Yin Hsu, Ph.D.

      Affiliations

    • Department of Life Science, Tzu Chi University, Hualien, Taiwan
  • ,
  • Shu-Jun Chiu, Ph.D.

      Affiliations

    • Department of Life Science, Tzu Chi University, Hualien, Taiwan
    • Institute of Radiation Sciences, Tzu Chi Technology College, Hualien, Taiwan
    • Corresponding Author InformationReprint requests to: Shu-Jun Chiu, Ph.D., Department of Life Science, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan. Tel: 886-3-8565301, ext. 2631; Fax: 886-3-8572526

Received 22 September 2009 ,Revised 16 October 2009 ,Accepted 10 December 2009.

References 

  1. Suzuki M, Boothman DA. Stress-induced premature senescence (SIPS): Influence of SIPS on radiotherapy. J Radiat Res (Tokyo). 2008;49:105–112
  2. Roninson IB, Broude EV, Chang BD. If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resist Updat. 2001;4:303–313
  3. Verheij M. Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev. 2008;27:471–480
  4. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: Relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995;33:781–796
  5. Bhonde MR, Hanski ML, Notter M, et al. Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth. Oncogene. 2006;25:165–175
  6. Schmitt CA. Cellular senescence and cancer treatment. Biochim Biophys Acta. 2007;1775:5–20
  7. Campisi J. d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729–740
  8. Aliouat-Denis CM, Dendouga N, Van den Wyngaert I, et al. p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2. Mol Cancer Res. 2005;3:627–634
  9. Gewirtz DA, Holt SE, Elmore LW. Accelerated senescence: An emerging role in tumor cell response to chemotherapy and radiation. Biochem Pharmacol. 2008;76:947–957
  10. Beausejour CM, Krtolica A, Galimi F, et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003;22:4212–4222
  11. Olsen CL, Gardie B, Yaswen P, et al. Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion. Oncogene. 2002;21:6328–6339
  12. Michaloglou C, Vredeveld LC, Soengas MS, et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005;436:720–724
  13. Chang BD, Broude EV, Dokmanovic M, et al. A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res. 1999;59:3761–3767
  14. Jallepalli PV, Waizenegger IC, Bunz F, et al. Securin is required for chromosomal stability in human cells. Cell. 2001;105:445–457
  15. Romero F, Multon MC, Ramos-Morales F, et al. Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase. Nucleic Acids Res. 2001;29:1300–1307
  16. Nagao K, Adachi Y, Yanagida M. Separase-mediated cleavage of cohesin at interphase is required for DNA repair. Nature. 2004;430:1044–1048
  17. Zhou Y, Mehta KR, Choi AP, et al. DNA damage-induced inhibition of securin expression is mediated by p53. J Biol Chem. 2003;278:462–470
  18. Romero F, Gil-Bernabe AM, Saez C, et al. Securin is a target of the UV response pathway in mammalian cells. Mol Cell Biol. 2004;24:2720–2733
  19. Chiu SJ, Hsu TS, Chao JI. Opposing securin and p53 protein expression in the oxaliplatin-induced cytotoxicity of human colorectal cancer cells. Toxicol Lett. 2006;167:122–130
  20. Bernal JA, Roche M, Mendez-Vidal C, et al. Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin. Cell Death Differ. 2008;15:202–212
  21. Heaney AP, Singson R, McCabe CJ, et al. Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet. 2000;355:716–719
  22. Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006;4:130–137
  23. Solbach C, Roller M, Fellbaum C, et al. PTTG mRNA expression in primary breast cancer: a prognostic marker for lymph node invasion and tumor recurrence. Breast. 2004;13:80–81
  24. Solbach C, Roller M, Eckerdt F, et al. Pituitary tumor-transforming gene expression is a prognostic marker for tumor recurrence in squamous cell carcinoma of the head and neck. BMC Cancer. 2006;6:242
  25. Chiu SJ, Chao JI, Lee YJ, et al. Regulation of gamma-H2AX and securin contribute to apoptosis by oxaliplatin via a p38 mitogen-activated protein kinase-dependent pathway in human colorectal cancer cells. Toxicol Lett. 2008;179:63–70
  26. Chang BD, Swift ME, Shen M, et al. Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci U S A. 2002;99:389–394
  27. Rubinek T, Chesnokova V, Wolf I, et al. Discordant proliferation and differentiation in pituitary tumor-transforming gene-null bone marrow stem cells. Am J Physiol Cell Physiol. 2007;293:C1082–C1092
  28. Di X, Shiu RP, Newsham IF, et al. Apoptosis, autophagy, accelerated senescence and reactive oxygen in the response of human breast tumor cells to adriamycin. Biochem Pharmacol. 2009;77:1139–1150
  29. Rogakou EP, Pilch DR, Orr AH, et al. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–5868
  30. Downey M, Durocher D. gammaH2AX as a checkpoint maintenance signal. Cell Cycle. 2006;5:1376–1381
  31. Keogh MC, Kim JA, Downey M, et al. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2006;439:497–501
  32. Antoni L, Sodha N, Collins I, et al. CHK2 kinase: Cancer susceptibility and cancer therapy–two sides of the same coin?. Nat Rev Cancer. 2007;7:925–936
  33. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426:194–198
  34. Xu Y. Induction of genetic instability by gain-of-function p53 cancer mutants. Oncogene. 2008;27:3501–3507
  35. Chen G, Li J, Li F, et al. Inhibitory effects of anti-sense PTTG on malignant phenotype of human ovarian carcinoma cell line SK-OV-3. J Huazhong Univ Sci Technolog Med Sci. 2004;24:369–372
  36. Solbach C, Roller M, Peters S, et al. Pituitary tumor-transforming gene (PTTG): A novel target for anti-tumor therapy. Anticancer Res. 2005;25:121–125
  37. El-Naggar SM, Malik MT, Kakar SS. Small interfering RNA against PTTG: A novel therapy for ovarian cancer. Int J Oncol. 2007;31:137–143
  38. Chesnokova V, Wong C, Zonis S, et al. Diminished pancreatic beta-cell mass in securin-null mice is caused by beta-cell apoptosis and senescence. Endocrinology. 2009;150:2603–2610

 Wen-Shu Chen and Yi-Chu Yu contributed equally to this work.

 This work was supported by a grant from the National Science Council, Taiwan (NSC 96-2321-B-320-001-MY3).

 Conflict of interest: none.

PII: S0360-3016(09)03678-5

doi: 10.1016/j.ijrobp.2009.12.013

International Journal of Radiation Oncology * Biology * Physics
Volume 77, Issue 2 , Pages 566-574 , 1 June 2010