Telomerase activity and expression of telomerase reverse transcriptase correlated with cell proliferation in meningiomas and malignant brain tumors in vivo

Abstract.

Telomerase activity was examined in intracranial tumors and compared with gene expression of the two core components of telomerase – the reverse transcriptase subunit (hTERT) and the RNA subunit (hTR) – and the proliferative index. We investigated 32 tumors across three to five sampled regions (20 meningiomas, 1 acoustic schwannoma, 1 pituitary adenoma, 8 gliomas, and 2 medulloblastomas). Telomerase activity was demonstrated by the telomeric repeat amplification protocol (TRAP) assay in seven (22%) intracranial tumors (four malignant brain tumors, two atypical meningiomas and one ependymoma) but could not be detected in the 18 (100%) benign meningiomas. hTERT and hTR mRNA were detected using reverse-transcription polymerase chain reaction (RT-PCR). hTERT mRNA was present in 20 (63%) intracranial tumors. Whereas hTERT mRNA transcripts were consistently low or absent in meningiomas, malignant brain tumors exhibited elevated hTERT mRNAs. Multiple regions of glioblastomas showed differences in telomerase activity and in the presence of hTERT mRNA. RT-PCR analysis revealed, for the first time in intracranial tumors, the presence of hTERT mRNA spliced products, corresponding to full-length mRNA as well as spliced mRNAs with critical reverse transcriptase motifs deleted. Only tumors with marked telomerase activity showed all hTERT spliced messages simultaneously. The absence of a positive correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT spliced variants. We found a significant correlation between telomerase activity scores and Ki-67 proliferation index. A positive association is also seen between Ki-67 staining and the degree of hTERT mRNA expression. This shows that there seems to be a relationship between telomerase activity or the degree of hTERT expression and proliferation rate in intracranial tumors.