| Functional impairment of telomerase in sublines derived from human lung adenocarcinoma exposed to mild oxidative stress. | |
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MedLine Citation:
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PMID: 16004965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the effects of a sublethal concentration of H(2)O(2) on cancer cells by using sublines derived from human lung adenocarcinoma cell line A549 cells exposed to 200 microM H(2)O(2). These sublines (AST cells) showed an elongated morphology distinct from the rounded morphology of A549 cells. Notably, AST cells demonstrated telomere shortening despite displaying telomerase activity and expressing human telomerase reverse transcriptase (hTERT). This functional impairment of telomerase occurred due to perturbed subcellular localization of hTERT in AST cells. Endogenous as well as ectopically expressed hTERT was localized in the nuclei of A549 cells; however, in AST cells, the localization was mainly in the cytoplasm. Furthermore, these AST cells demonstrated decreased tumorigenic features both in vitro and in vivo. These results suggest that depletion of hTERT from nuclei not only endows cancer cells with a finite replicative life span accompanied by telomere shortening, but also decreases the tumorigenicity of cancer cells. |
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Authors:
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Yoshinori Katakura; Kaichi Yoshizaki; Tomoharu Yasuda; Takahiro Tsunematsu; Norihisa Uehara; Takumi Miura; Tsukasa Fujiki; Sanetaka Shirahata |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 334 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-07-22 Completed Date: 2005-09-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 450-9 Citation Subset: IM |
Affiliation:
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Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. katakura@grt.kyushu-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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enzymology*,
pathology* Cell Line, Tumor Cell Proliferation / drug effects Cell Size / drug effects Enzyme Activation / drug effects Humans Hydrogen Peroxide / pharmacology* Lung Neoplasms / enzymology*, pathology* Oxidative Stress* Phenotype Telomerase / metabolism* Telomere / drug effects, ultrastructure |
| Chemical | |
Reg. No./Substance:
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7722-84-1/Hydrogen Peroxide; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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