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.
Keywords
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Article info
Publication history
Accepted:
March 21,
2006
Received in revised form:
January 23,
2006
Received:
September 6,
2005
Footnotes
☆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.).
Identification
Copyright
© 2006 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
