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

2000; Springer Nature; Volume: 82; Issue: 11 Linguagem: Inglês

10.1054/bjoc.2000.1117

1532-1827

Norihiro Sato, Kazuhiro Mizumoto, Masahiro Kusumoto, Shoko Nishio, Naoki Maehara, Taro Urashima, Takahiro Ogawa, Masao Tanaka,

RNA Interference and Gene Delivery

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 microM) 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.