title: Telomerase inhibition impairs tumor growth in glioblastoma xenografts.
abstract: 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.
authors.affiliation: Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy. marialaura.falchetti@inmm.cnr.it
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Falchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorenzo
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Mongiardi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Petrucci
authors.forename: Nicola
authors.initials: N
authors.lastname: Montano
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierconti
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Andrea
authors.initials: A
authors.lastname: Levi
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
mesh_terms: 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
chemical_list: D019098:Telomerase