On the significance of telomerase activity in human malignant glioma cells

Telomerase is critical for tumor cell immortalization and is a novel target for cancer chemotherapy. Here, we examined whether telomerase is expressed in glioma cell lines, whether telomerase activity is regulated by bcl-3 or p53, and whether telomerase activity predicts response to chemotherapy. Fu rther, we characterized the effects of a candidate telomerase inhibitor, pe nclomedine, in glioma cells. All 12 human malignant glioma cell lines exami ned were telomerase positive. Telomerase activity was not modulated during cell cycle progression, did not correlate with p53 status or bcl-2 family p rotein expression, and did not predict drug sensitivity, except for an asso ciation with resistance to carmustine. Ectopic bcl-2 expression did not enh ance telomerase activity. Wild-type p53 reduced telomerase activity in cell lints retaining p53 activity but not in p53-mutant cell lines. Penclomedin e killed glioma cells via an apoptotic, but death receptor-, bcl-2- and cas pase-independent pathway, but did not inhibit telomerase and did not act sy nergistically with cytotoxic drugs. We conclude that telomerase activity do es not account for the differential chemosensitivity of human glioma cells and that penclomedine kills glioma cells via a telomerase-independent pathw ay. (C) 2000 Elsevier Science B.V. All rights reserved.