Telomerase inhibition impairs tumor growth in glioblastoma xenografts

Maria Laura Falchetti, Paolo Fiorenzo, Maria Patrizia Mongiardi, Giovanna Petrucci, Nicola Montano, Giulio Maira, Francesco Pierconti, Luigi Maria Larocca, Andrea Levi, Roberto Pallini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)532-537
Number of pages6
JournalNeurological Research
Volume28
Issue number5
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Glioblastoma multiforme
  • RNA interference
  • Telomerase
  • Tumor xenograft

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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  • Cite this

    Falchetti, M. L., Fiorenzo, P., Mongiardi, M. P., Petrucci, G., Montano, N., Maira, G., Pierconti, F., Larocca, L. M., Levi, A., & Pallini, R. (2006). Telomerase inhibition impairs tumor growth in glioblastoma xenografts. Neurological Research, 28(5), 532-537. https://doi.org/10.1179/016164106X116818