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Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells

Lookup NU author(s): Dr Gabriele Saretzki, Professor Thomas von Zglinicki

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Abstract

Telomerase is a promising target for human cancer gene therapy. Its inhibition allows telomere shortening to occur in cancer cells, which in turn is thought to trigger delayed senescence and/or apoptosis. We tested whether telomerase inhibition might have additional, immediate effects on tumor cell growth. Ovarian cancer cell lines with widely differing telomere lengths were efficiently transduced with an adenovirus expressing a ribozyme directed against the T motif of the catalytic subunit of human telomerase, hTERT. Three days after transduction, telomerase activity was significantly reduced and massive cell loss was induced in mass cultures from all four ovarian cancer cell lines tested, whereas transduction of telomerase-negative human fibroblasts did not attenuate their growth. The kinetics of induction of cell death in cancer cells was not significantly dependent on telomere length, and telomeres did not shorten measurably before the onset of apoptosis. The data suggest the existence of a "fast-track" mechanism by which diminution of telomerase can interfere with cancer cell growth and induce cell death, presumably by apoptosis. This phenomenon might be a consequence of the telomere capping function provided by telomerase in tumor cells. Uncapping of telomeres by ribozyme-mediated inhibition of telomerase bears therapeutic potential for ovarian cancer.


Publication metadata

Author(s): Saretzki G; Von Zglinicki T; Ludwig A; Runnebaum IB

Publication type: Article

Publication status: Published

Journal: Cancer Gene Therapy

Year: 2001

Volume: 8

Issue: 10

Pages: 827-834

ISSN (print): 0929-1903

ISSN (electronic): 1476-5500

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.cgt.7700383

DOI: 10.1038/sj.cgt.7700383

PubMed id: 11687906


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