Rapid Inhibition of Cancer Cell Growth Induced by Lentiviral Delivery and Expression of Mutant-Template Telomerase RNA and Anti-telomerase Short-Interfering RNA
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- Shang Li
- 1Biochemistry and Biophysics and Departments of
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- Jonathan E. Rosenberg
- 1Biochemistry and Biophysics and Departments of
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- Annemarie A. Donjacour
- 2Anatomy, University of California at San Francisco, San Francisco, California
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- Inna L. Botchkina
- 1Biochemistry and Biophysics and Departments of
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- Yun Kit Hom
- 2Anatomy, University of California at San Francisco, San Francisco, California
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- Gerald R. Cunha
- 2Anatomy, University of California at San Francisco, San Francisco, California
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- Elizabeth H. Blackburn
- 1Biochemistry and Biophysics and Departments of
抄録
<jats:title>Abstract</jats:title> <jats:p>In human cancers, telomeres are commonly maintained by elevated levels of the ribonucleoprotein enzyme telomerase, which contains an intrinsic templating RNA moiety (human telomerase RNA; hTER) and the core protein (human telomerase reverse transcriptase). We developed a lentiviral system for efficient overexpression of mutant-template human telomerase RNA (MT-hTer) to add mutant DNA to telomeres in cancer cells. We show that such MT-hTer overexpression rapidly inhibits cell growth and induces apoptosis in telomerase-positive precancerous or cancer cells but not in telomerase-negative cells. These rapid effects occurred independent of wild-type p53 and telomere length. Tumor growth and progression were significantly decreased in xenografts of human tumor cells overexpressing MT-hTers. Expression of a hairpin short-interfering RNA that specifically targeted the endogenous wild-type hTER template region, but spared the MT-hTers, also caused p53-independent cell growth inhibition and apoptosis, and when coexpressed with MT-hTer, synergistically killed cancer cells. Hence, anti-wild-type-hTER short-interfering RNA and MT-hTers may act through distinct pathways and, particularly in combination, represent a promising approach to anticancer therapies.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 64 (14), 4833-4840, 2004-07-15
American Association for Cancer Research (AACR)
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詳細情報 詳細情報について
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- CRID
- 1360574095635555200
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- NII論文ID
- 30018590180
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- ISSN
- 15387445
- 00085472
- http://id.crossref.org/issn/00085472
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