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 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.
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Authors | N Sato, K Mizumoto, M Kusumoto, S Nishio, N Maehara, T Urashima, T Ogawa, M Tanaka |
Journal | British journal of cancer
(Br J Cancer)
Vol. 82
Issue 11
Pg. 1819-26
(Jun 2000)
ISSN: 0007-0920 [Print] England |
PMID | 10839297
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- DNA Primers
- Etoposide
- Telomerase
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Base Sequence
- DNA Primers
- Etoposide
(pharmacology)
- Humans
- Pancreatic Neoplasms
(enzymology, pathology)
- Reverse Transcriptase Polymerase Chain Reaction
- Telomerase
(genetics, metabolism)
- Tumor Cells, Cultured
- Up-Regulation
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