TRF2 inhibition triggers apoptosis and reduces tumourigenicity of human melanoma cells

Annamaria Biroccio, Angela Rizzo, Raffaella Elli, Catherine Elaine Koering, Aurélie Belleville, Barbara Benassi, Carlo Leonetti, Malcolm F G Stevens, Maurizio D'Incalci, Gabriella Zupi, Eric Gilson

Research output: Contribution to journalArticlepeer-review

Abstract

The inhibition of the telomere-binding protein TRF2, by expressing the dominant negative form TRF2ΔBΔC, has been used as a model of anti-telomere strategy to induce a reversion of the malignant phenotype of M14 and JR5 human melanoma lines. Over-expression of TRF2ΔBΔC induced apoptosis and reduced tumourigenicity exclusively in JR5 cells. p53 and Rb status and apoptotic response to DNA damage did not seem to account for the different response of the two lines to TRF2 inhibition. Interestingly, JR5 cells possess shorter and more dysfunctional telomeres compared to M14 line. Moreover, the treatment with the G-quadruplex-interacting agent (G4-ligand) RHPS4 sensitises M14 cells to TRF2 inhibition. These results demonstrate that TRF2 can impair tumuorigenicity of human cancer cells. They further suggest that a basal level of telomere instability favours an efficient response to TRF2 inhibition and that a combined anti-TRF2 and G4-ligand therapy would have synergistic inhibitory effects on tumour cell growth.

Original languageEnglish
Pages (from-to)1881-1888
Number of pages8
JournalEuropean Journal of Cancer
Volume42
Issue number12
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Anti-telomere therapy
  • G4-ligand
  • TRF2

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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