title: TRF2 inhibition triggers apoptosis and reduces tumourigenicity of human melanoma cells.
abstract: The inhibition of the telomere-binding protein TRF2, by expressing the dominant negative form TRF2(DeltaBDeltaC), 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 TRF2(DeltaBDeltaC) 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.
authors.affiliation: Experimental Chemotherapy Laboratory, Experimental Research Centre, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, Rome 00158, Italy. biroccio@ifo.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: Biroccio
authors.forename: Angela
authors.initials: A
authors.lastname: Rizzo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Elli
authors.forename: Catherine-Elaine
authors.initials: CE
authors.lastname: Koering
authors.forename: Aurélie
authors.initials: A
authors.lastname: Belleville
authors.forename: Barbara
authors.initials: B
authors.lastname: Benassi
authors.forename: Carlo
authors.initials: C
authors.lastname: Leonetti
authors.forename: Malcolm F G
authors.initials: MF
authors.lastname: Stevens
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.forename: Gabriella
authors.initials: G
authors.lastname: Zupi
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015139:Blotting, Southern; D015153:Blotting, Western; D005822:Genetic Vectors; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000628:therapy; D009368:Neoplasm Transplantation; D016615:Telomere / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53