Telomerase inhibition induces acute ATM-dependent growth arrest in human astrocytomas
Vincent C H Wong1, Jing Ma, Cynthia E Hawkins
1Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada M5G 1X8.
Abstract:
The purpose of the study was to examine the degree of hTERT, the catalytic subunit of telomerase, expression in paediatric high-grade astrocytoma and to explore the potential of telomerase inhibition as a therapy for these tumours. hTERT was expressed at high levels in 36 of 44 paediatric astrocytomas. Telomerase inhibition induced acute DNA damage and ATM-pathway-dependent G2/M cell cycle arrest in astrocytomas in vitro, both occurring prior to telomere shortening itself. Our data suggest that telomerase inhibition could be a useful adjuvant therapy for high-grade astrocytomas, potentially inducing tumour growth arrest following short-term treatment.
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