Telomerase inhibition impairs tumor growth in glioblastoma xenografts.
Telomerase is a specialized DNA polymerase that is required to replicate the ends of linear chromosomes, the telomeres. The majority of human cancers express high levels of telomerase activity that is permissive for tumor growth because it provides cells with an extended proliferative potential. Additionally, telomerase exerts cell growth promoting functions and favors cell survival. Human glioblastoma multiforme (GBM) cells express high level of telomerase activity owing to the overexpression of human telomerase reverse transcriptase (hTERT), the limiting subunit of the enzyme. Here we used retroviral mediated RNA interference to dampen down telomerase activity in two distinct human GBM cell lines, U87MG and TB10. Substantial decrease of hTERT mRNA and telomerase activity had only minimal effects on telomere length maintenance, cell growth and survival in vitro. On the contrary, development of tumors upon subcutaneously grafting of U87MG and TB10 cells and intracranial implantation of U87MG cells in nude athymic mice was strongly reduced by telomerase inhibition.
Falchetti
Maria Laura
ML
Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy. marialaura.falchetti@inmm.cnr.it
Fiorenzo
Paolo
P
Mongiardi
Maria Patrizia
MP
Petrucci
Giovanna
G
Montano
Nicola
N
Maira
Giulio
G
Pierconti
Francesco
F
Larocca
Luigi Maria
LM
Levi
Andrea
A
Pallini
Roberto
R
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous
D019098:Telomerase