Telomerase inhibition impairs tumor growth in glioblastoma xenografts
Authors: Falchetti, Maria Laura1; Fiorenzo, Paolo1; Mongiardi, Maria Patrizia1; Petrucci, Giovanna2; Montano, Nicola2; Maira, Giulio2; Pierconti, Francesco3; Larocca, Luigi Maria3; Levi, Andrea1; Pallini, Roberto2
Source: Neurological Research, Volume 28, Number 5, July 2006 , pp. 532-537(6)
Publisher: Maney Publishing
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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.Keywords: GLIOBLASTOMA MULTIFORME; TELOMERASE; RNA INTERFERENCE; TUMOR XENOGRAFT
Document Type: Research article
DOI: 10.1179/016164106X116818
Affiliations: 1: Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy 2: Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy 3: Institute of Pathology, Catholic University School of Medicine, Rome, Italy
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