Importance of telomerase and its core subunits in glioma

Life Sciences 2007 (2007) Proc Life Sciences, PC317

Poster Communications: Importance of telomerase and its core subunits in glioma

R. Patel1, N. Cruickshanks1, C. Lu1, A. Shervington 1

1. Biological Sciences, University of Central Lancashire, Preston, Lancashire, United Kingdom.

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Expression of telomerase influences the effectiveness of treatment in cancers. Telomerase is composed of two core subunits, telomerase reverse transcriptase (hTERT) and an RNA subunit (hTR) (Dong et al., 2005), the enzyme functions by utilizing hTR products as a template for the synthesis of new telomeric repeat sequences (Wong and Collins, 2003). The molecular chaperone Hsp90 regulates the maturation, stability and folding of telomerase. It is part of a foldosome, which is required for telomerase activation. An increase in telomerase activity has been shown to correspond with an increase in the molecular chaperones required for the foldosome (Holt et al, 1999). Therefore studying the expression of hTERT and hsp90 in glioma cell lines and tissues may aid the pathological measurements of the disease and may provide a more accurate patient prognosis. The aim of our research was to analyse the expression of hTERT and hsp90 (α and β subunits) in glioma cell lines and tissues using quantitative RT-PCR and to detect telomerase activity. We found that all cancerous cell lines and tissues expressed hTERT and both subunits of hsp90. The control cell line NHA (Normal human Astrocyte) and the normal brain tissues did not expresses hTERT and very low levels of hsp90 (α and β) was detected in the normal samples. Telomerase activity in cell lines was consistent with hTERT expression but in the tissues only 43% of the cancerous tissues showed active telomerase. Several small molecule inhibitors of Hsp90 have been identified that can deplete cellular levels of multiple oncogenic client proteins simultaneously by enhancing their ubiquitination and proteasome-mediated degradation. The activity of Hsp90 inhibitors has been well validated in preclinical cancer models. We are aiming to assess some of these inhibitors on glioma cell lines and tissues. Given the redundancy and complexity of the molecular abnormalities present in most cancers, the ability of Hsp90 inhibitors to alter the activity of multiple oncogenic targets may provide a unique therapeutic benefit to patients.



Where applicable, experiments conform with Society ethical requirements.

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