TY - JOUR
T1 - TRF2 inhibition triggers apoptosis and reduces tumourigenicity of human melanoma cells
AU - Biroccio, Annamaria
AU - Rizzo, Angela
AU - Elli, Raffaella
AU - Koering, Catherine Elaine
AU - Belleville, Aurélie
AU - Benassi, Barbara
AU - Leonetti, Carlo
AU - Stevens, Malcolm F G
AU - D'Incalci, Maurizio
AU - Zupi, Gabriella
AU - Gilson, Eric
PY - 2006/8
Y1 - 2006/8
N2 - 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.
AB - 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.
KW - Anti-telomere therapy
KW - G4-ligand
KW - TRF2
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U2 - 10.1016/j.ejca.2006.03.010
DO - 10.1016/j.ejca.2006.03.010
M3 - Article
C2 - 16750909
AN - SCOPUS:33746599027
VL - 42
SP - 1881
EP - 1888
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 12
ER -