Expression profile of telomerase subunits in human pleural mesothelioma

Using the TRAP assay, telomerase activity was previously detected in over 9 0% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultur es (MCCs), suggesting that telomerase re-activation occurs during multi-ste p mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein ( hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs an d 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in s ix MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly ex-pressed in all mal ignant and non-malignant serosal cells and tissues. Three alternatively spa ced hTERT transcripts were detected in all telomerase-positive samples, whe reas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These re sults indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expres sion can play a critical role in MM carcinogenesis, While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-mali gnant serosal lesions, Copyright (C) 2000 John Whey & Sons, Ltd.