| Adenovirus-mediated transfer of caspase-3 with Fas ligand induces drastic apoptosis in U-373MG glioma cells. | |
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MedLine Citation:
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PMID: 10772815 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Impaired function of apoptosis-related genes is deeply involved in oncogenesis and the progression of cancers, and caspase-3 plays a critical role as an executioner of apoptosis. We introduced the caspase-3 gene via an adenovirus (Adv) vector into Alexander hepatoma cells, MCF-7 breast cancer cells, and U251 and U-373MG glioma cells which have different endogenous levels of caspase-3 expression. None of the cell lines underwent apoptosis by overexpression of caspase-3, indicating that induction of caspase-3 alone is not applicable for cancer gene therapy. Next, we investigated whether overexpression of caspase-3 could enhance Fas ligand-mediated apoptosis in these four cell lines. In U-373MG cells, which showed the highest level of expression of surface Fas among the four cell lines, coinfection of the Adv for caspase-3 (Adv-caspase-3) and the Adv for Fas ligand (Adv-FL) induced a remarkably increased degree of apoptosis compared with that induced by the single infection of either Adv-caspase-3 or Adv-FL. Similar results were obtained by cotreatment with anti-Fas antibody in U-373MG cells. These data suggest that when strong proapoptotic upstream stimuli are induced, the level of caspase-3 expression determines the degree of apoptosis in cancer cell lines. In conclusion, overexpression of caspase-3 alone did not induce apoptosis in cancer cells. Both a strong proapoptotic signal and a high expression of caspase-3 were required to induce drastic apoptosis in cancers. This strategy would be highly beneficial for selected cancer patients. |
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Authors:
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N Shinoura; Y Muramatsu; Y Yoshida; A Asai; T Kirino; H Hamada |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental cell research Volume: 256 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-05-18 Completed Date: 2000-05-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 423-33 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Academic Press. |
Affiliation:
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Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics* Antigens, CD95 / genetics, metabolism* Apoptosis* Breast Neoplasms Carcinoma, Hepatocellular Caspase 3 Caspases / genetics, metabolism* Enzyme Precursors / genetics, metabolism* Female Gene Transfer Techniques* Glioma Humans Immunoblotting Ligands Microscopy, Electron Poly(ADP-ribose) Polymerases / metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Enzyme Precursors; 0/Ligands; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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