Abstract
To understand the roles of bcl-2 for the survival of leukemic cells, we constructed human leukemic HL60 transformant lines in which full length bcl-2 antisense message was conditionally expressed by a tetracycline-regulatable expression system. Cell growth was completely inhibited after antisense message induction and massive cell death was induced. Electron microscopic examinations show that cells died by autophagy, but not by apoptosis. The morphology and the function of mitochondria remained intact: neither the reduction in mitochondrial membrane potential nor the nuclear translocation of AIF, a mitochondrial protein that translocates to nuclei in cases of apoptosis, was observed. Caspase inhibitors did not rescue bcl-2-antisense-mediated autophagy. Thus, bcl-2 is essential for leukemic cell survival and its down-regulation results in autophagy. Cell Death and Differentiation (2000) 7, 1263 - 1269.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / pharmacology
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Antigens, CD34 / immunology
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Antigens, CD34 / metabolism
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Apoptosis / drug effects
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Apoptosis / physiology
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Autophagy / drug effects
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Autophagy / genetics*
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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Caspases / genetics
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Caspases / metabolism*
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Down-Regulation / drug effects
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Down-Regulation / genetics*
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Doxycycline / pharmacology
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Gene Expression Regulation, Leukemic / drug effects
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Gene Expression Regulation, Leukemic / physiology
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HL-60 Cells / drug effects
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HL-60 Cells / metabolism*
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HL-60 Cells / ultrastructure
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Humans
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Leukemia / genetics
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Leukemia / metabolism*
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Leukemia / physiopathology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Antisense / drug effects
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RNA, Antisense / metabolism
Substances
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Anti-Bacterial Agents
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Antigens, CD34
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Proto-Oncogene Proteins c-bcl-2
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RNA, Antisense
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Caspases
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Doxycycline