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. 2000 Jun;82(11):1819–1826. doi: 10.1054/bjoc.2000.1117

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

N Sato 1, K Mizumoto 1, M Kusumoto 1, S Nishio 1, N Maehara 1, T Urashima 1, T Ogawa 1, M Tanaka 1
PMCID: PMC2363240  PMID: 10839297

Abstract

Telomerase plays a critical role in the development of cellular immortality and oncogenesis. Activation of telomerase occurs in a majority of human malignant tumours, and the relation between telomerase and vulnerability to drug-mediated apoptosis remains unclear. In this study, we demonstrate, for the first time, up-regulation of telomerase activity in human pancreatic cancer cells treated with etoposide, a topoisomerase II inhibitor. Exposure of MIA PaCa-2 cells to etoposide at various concentrations (1–30 μM) resulted in two- to threefold increases in telomerase activity. Up-regulation was detectable 24 h after drug exposure and was accompanied by enhanced expression of mRNA of the human telomerase reverse transcriptase. Telomerase activation 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 telomerase activity and the percentage of dead cells after etoposide treatment. These findings suggest the existence of an anti-apoptotic pathway through which telomerase is up-regulated in response to DNA damage. This telomerase activation pathway may be one of the mechanisms responsible for the development of etoposide resistance in certain pancreatic cancer cells. © 2000 Cancer Research Campaign

Keywords: telomerase, topoisomerase II inhibitor, DNA damage, hTERT, apoptosis, drug resistance

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Selected References

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