Study On Telomerase In Glioma

Object:Telomerase activity is involved in the maintenance of telomere length and is thought to be required for cellular immortality and oncogenesis. The goal of the present study was to assess and correlate the telomerase activity and proliferative activity in gliomas of different grades ,and to determine the role of telomerase and telomere maintain in mechnism of glioma development, with detecting the telomerase activity ,expression of telomerase genes and length of telomere in gliomas.Methods:Forty rapidly surgical resected glioma specimens,3 glioma cell lines and 5 normal brain tissue were used to study the telomerase activity by semi-quantitative telomeric repeat amplification protocol (TRAP) silver-staining. We also investigated the proliferative activity of gliomas by Ki-67 immunolabelling; Three of major subunits composing telomerase ,human telomerase RNA(hTR), telomerase-associated protein(TP 1 )and telomerase catalytic subunits(hTRT) were analyzed by semi-quantitative RT-PCR. Meanwhile, DNAs extracted from normal and tumor samples were studied by southern blot anlysis with(TTAGGG)3 probe specific for human telomeric sequences.Results:Telomerase activity was detected in all glioma cell lines , 33of 40(82.5%) gliomas specimens and none of normal brain tissue,telomerase expression was associated with grade of tumor and Ki-67 immunolabelling. There was a significant correlation of telomerase activity with hTRT rnRNA expression but not with TPI and hTR expression. The length of telomere in maligant gliomas is shorter than that in normal glia cells.and thetelomere length is correlated with telomerase activity.Conclusions:Our findings suggest that telomerase activity could be a special marker of gliomas and an index of maligant potential. Expression of hTRT is specific to cancer lessions and appears to be a rate-limiting determinant of the enzymatic activity of human telomerase. Up-regulation of hTRT may play a critically important role in the development of cell immortality and telomerase reactive.while hTR is required for telomerase but not sufficient by itself, and it抯 expression level is not corrected with telomerase activity. Telomere reduction is one of the important genetic events during transformation of gliomas. Telomere repair mechanism may be initiated in glioma which may maintain a relative stability of TRFs and permit a constitutive proliferation of these malignant cells.