| Research Abstract |
Deregulation of the G1 cell cycle checkpoint, which leads to unregulated proliferation of tumor cells, is presumed to be an essential step for glioma progression toward high-grade gliomas. Another important step is the immortalization of the cells, in which activation of telomerase plays an essential role. Because these two key steps should occur concomitantly in theory, we investigated the correlation of cell cycle checkpoint deregulation and telomerase activity in glioma cells and in glioma samples.
p16/CDKN2A gene incorporated in adenovirus vector was transfected into two glioblastoma cell lines, T98G and U251. The telomerase activity measured by the stretch-PCR assay was markedly decreased in u251 cells and completely suppressed in T98G cells, indicating that activation of telomerase may be a consequence of the G1 checkpoint deregulation.
We next examined three genetic alterations, p16 deletion, 13q LOH for RB inactivation, and CDK4 gene amplification in various grades of gliomas. At least one of those three genetic alterations was found in 80% of grade4, 20% of grade 3 and 5% of grad2tumors. However, we could detect telomerase activity in only half of grade 4 tumors, and there was no obvious correlation with the genetic alterations. There still is a possibility that difference in sampling procedured may have affected the results, our data were rather negative for the possible correlation of the cell cycle deregulation with the telomerase activation.
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