Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway
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作者:
McNeish, IA
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
McNeish, IA
[1
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Bell, S
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
Bell, S
[1
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McKay, T
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
McKay, T
[1
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Tenev, T
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
Tenev, T
[1
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Marani, M
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
Marani, M
[1
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Lemoine, NR
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Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
Lemoine, NR
[1
]
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[1] Hammersmith Hosp, Imperial Coll Sch Med, Canc Res UK Mol Oncol Unit, London W12 0NN, England
We have constructed Ad CMV-Smac, a recombinant adenovirus encoding Smac/DIABLO, the recently described second mitochondrial activator of caspases. Transfection of ovarian carcinoma cells with Ad CMV-Smac at multiplicities of infection of 3-60 pfu/cell leads to increasing apoptosis in a dose-dependent manner. Western blot analysis confirms that Smac-induced apoptosis proceeds via a pathway mediated primarily by caspase-9 that can be inhibited by zLEHD-fmk and overexpression of the X-linked inhibitor of apoptosis protein (XIAP). In contrast, there is no cleavage of either caspase-8 or caspase-12. Ad CMV-Smac appears to induce apoptosis independently of cytochrome c release from mitochondria and is not inhibited by overexpression of Bcl-2. Ad CMV-Smac can combine with other proapoptotic factors, such as cisplatin, paclitaxel, and procaspase-3, to produce greater levels of apoptosis in transfected cells. (C) 2003 Elsevier Science (USA). All rights reserved.
机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Fadeel, B
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Hassan, Z
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Hassan, Z
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Hellström-Lindberg, E
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Hellström-Lindberg, E
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Henter, JI
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Henter, JI
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Orrenius, S
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Orrenius, S
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Zhivotovsky, B
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Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, SwedenKarolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Fujita, E
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Egashira, J
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Egashira, J
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Urase, K
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Urase, K
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Kuida, K
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Kuida, K
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Momoi, T
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Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, JapanNatl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Fadeel, B
;
Hassan, Z
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Hassan, Z
;
Hellström-Lindberg, E
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Hellström-Lindberg, E
;
Henter, JI
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Henter, JI
;
Orrenius, S
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机构:Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
Orrenius, S
;
Zhivotovsky, B
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Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, SwedenKarolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Fujita, E
;
Egashira, J
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Egashira, J
;
Urase, K
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Urase, K
;
Kuida, K
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机构:Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan
Kuida, K
;
Momoi, T
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Natl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, JapanNatl Inst Neurosci, Div Dev & Differentiat, NCNP, Kodaira, Tokyo 1878502, Japan