Up-regulation of telomerase activity in human pancreatic cancer cells after exposure to etoposide

Telomerase plays a critical role in the development of cellular immortality and oncogenesis. Activation of telomerase occurs in a majority of human ma lignant tumours, and the relation between telomerase and vulnerability to d rug-mediated apoptosis remains unclear. In this study, we demonstrate, for the first time, up-regulation of telomerase activity in human pancreatic ca ncer cells treated with etoposide, a topoisomerase II inhibitor. Exposure o f MIA PaCa-2 cells to etoposide at various concentrations (1-30 mu M) resul ted in two- to threefold increases in telomerase activity. Up-regulation wa s detectable 24 h after drug exposure and was accompanied by enhanced expre ssion of mRNA of the human telomerase reverse transcriptase. Telomerase act ivation was also observed in AsPC-1 and PANC-1 cells but not in KP-3 and KP -1N cells. Furthermore, we found a negative correlation between increased t elomerase activity and the percentage of dead cells after etoposide treatme nt. These findings suggest the existence of an anti-apoptotic pathway throu gh which telomerase is up-regulated in response to DNA damage. This telomer ase activation pathway may be one of the mechanisms responsible for the dev elopment of etoposide resistance in certain pancreatic cancer cells. (C) 20 00 Cancer Research Campaign.