European Journal of Cancer
Volume 42, Issue 12 , Pages 1881-1888 , August 2006

TRF2 inhibition triggers apoptosis and reduces tumourigenicity of human melanoma cells

  • Annamaria Biroccio

      Affiliations

    • Experimental Chemotherapy Laboratory, “Experimental Research Centre”, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy
    • Corresponding Author InformationCorresponding author: Tel.: +39 6 52662569; fax: +39 6 52662592.
    • ,
  • Angela Rizzo

      Affiliations

    • Experimental Chemotherapy Laboratory, “Experimental Research Centre”, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy
    • ,
  • Raffaella Elli

      Affiliations

    • Cellular Biotechnology and Haematology Department, University “La Sapienza”, Rome, Italy
    • ,
  • Catherine-Elaine Koering

      Affiliations

    • Laboratoire de Biologie Moléculaire de la Cellule de l’Ecole Normale Supérieure, CNRS UMR5161, IFR128, Lyon, France
    • ,
  • Aurélie Belleville

      Affiliations

    • Laboratoire de Biologie Moléculaire de la Cellule de l’Ecole Normale Supérieure, CNRS UMR5161, IFR128, Lyon, France
    • ,
  • Barbara Benassi

      Affiliations

    • Experimental Chemotherapy Laboratory, “Experimental Research Centre”, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy
    • ,
  • Carlo Leonetti

      Affiliations

    • Experimental Chemotherapy Laboratory, “Experimental Research Centre”, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy
    • ,
  • Malcolm F.G. Stevens

      Affiliations

    • Center for Biomolecular Sciences, School of Pharmacy, The University of Nottingham, Nottingham, UK
    • ,
  • Maurizio D’Incalci

      Affiliations

    • Department of Oncology, Pharmacological Research Institute “Mario Negri”, Milan, Italy
    • ,
  • Gabriella Zupi

      Affiliations

    • Experimental Chemotherapy Laboratory, “Experimental Research Centre”, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy
    • ,
  • Eric Gilson

      Affiliations

    • Laboratoire de Biologie Moléculaire de la Cellule de l’Ecole Normale Supérieure, CNRS UMR5161, IFR128, Lyon, France
    • Service “Biologie des Tumeurs Solides – Génomique – Protéomique” Centre Hospitalier Lyon-Sud, France

Received 6 September 2005 ,Revised 23 January 2006 ,Accepted 21 March 2006.

References 

  1. de Lange T, Jacks T. For better or worse? Telomerase inhibition and cancer. Cell. 1999;98:273–275
  2. Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989;59:521–529
  3. Mergny JL, Riou JF, Mailliet P, Teulade-Fichou MP, Gilson E. Natural and pharmacological regulation of telomerase. Nucleic Acids Res. 2002;30:839–865
  4. Biroccio A, Leonetti C. Telomerase as a new target for the treatment of hormone-refractory prostate cancer. Endocr Relat Cancer. 2004;11:407–421
  5. Leonetti C, Amodei S, D’Angelo C, et al. Biological activity of the G-quadruplex ligand RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) is associated with telomere capping alteration. Mol Pharmacol. 2004;66:1138–1146
  6. Duan W, Rangan A, Vankayalapati H, et al. Design and synthesis of fluoroquinophenoxazines that interact with human telomeric G-quadruplexes and their biological effects. Mol Cancer Ther. 2001;1:103–120
  7. Zaug AJ, Podell ER, Cech TR. Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc Natl Acad Sci USA. 2005;102:10864–10869
  8. Griffith JD, Comeau L, Rosenfield S, et al. Mammalian telomeres end in a large duplex loop. Cell. 1999;97:419–422
  9. Broccoli D, Smogorzewska A, Chong L, de Lange T. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 1997;17:231–235
  10. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E. Telomeric localization of TRF2, a novel human telobox protein. Nat Genet. 1997;17:236–239
  11. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998;92:401–413
  12. Ancelin K, Brun C, Gilson E. Role of the telomeric DNA-binding protein TRF2 in the stability of human chromosome ends. BioEssay. 1998;20:879–883
  13. Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999;283:1321–1325
  14. Lechel A, Satyanarayana A, Ju Z, et al. The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo. EMBO Rep. 2005;6:275–281
  15. Celli GB, de Lange T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol. 2005;7:712–718
  16. Ancelin K, Brunori M, Bauwens S, et al. Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2. Mol Cell Biol. 2002;22:3474–3487
  17. Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered telomere state, not telomere loss. Science. 2002;295:2446–2449
  18. Wang RC, Smogorzewska A, de Lange T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell. 2004;119:355–368
  19. d’Adda di Fagagna F, Teo SH, Jackson SP. Functional links between telomeres and proteins of the DNA-damage response. Genes Dev. 2004;18:1781–1799
  20. Biroccio A, Amodei S, Benassi B, et al. Reconstitution of hTERT restores tumorigenicity in melanoma-derived c-Myc low-expressing clones. Oncogene. 2002;21:3011–3019
  21. Biroccio A, Benassi B, Filomeni G, et al. Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells. J Biol Chem. 2002;27:43763–43770
  22. Biroccio A, Gabellini C, Amodei S, et al. Telomere dysfunction increases cisplatin and ecteinascidin-743 sensitivity of melanoma cells. Mol Pharmcol. 2003;63:632–638
  23. Leonetti C, D’Agnano I, Lozupone F, et al. Antitumor effect of c-myc antisense phosphorothioate oligodeoxynucleotides on human melanoma cells in vitro and in mice. J Natl Cancer Inst. 1996;88:419–429
  24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta CT). Methods. 2001;25:402–408
  25. Chen X, Ko LJ, Jayaraman L, Prives C. p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev. 1996;10:2438–2451
  26. Yang Q, Zheng YL, Harris CC. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol Cell Biol. 2005;25:1070–1080
  27. Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000;25:347–352

☆ Grant support: Supported by grants from “Associazione Italiana Ricerca sul Cancro” (A.I.R.C.), “Ministero della Salute”, “CNR-MIUR”, “La Ligue Nationale contre le Cancer” and “Canceropole program EPIMED”. A. Rizzo is recipient of a fellowship from Italian Foundation for Cancer Research (F.I.R.C.).

PII: S0959-8049(06)00333-9

doi: 10.1016/j.ejca.2006.03.010

European Journal of Cancer
Volume 42, Issue 12 , Pages 1881-1888 , August 2006

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