Abstract
This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinase Kinases
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Cell Hypoxia / drug effects
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Cell Hypoxia / genetics
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Cell Line, Transformed
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell Survival / genetics
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Humans
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Protein Kinase Inhibitors / pharmacology
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Protein Kinases / drug effects
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Protein Kinases / metabolism*
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Ribonucleotides / pharmacology
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Sirolimus / pharmacology
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TOR Serine-Threonine Kinases
Substances
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Protein Kinase Inhibitors
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Ribonucleotides
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Aminoimidazole Carboxamide
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Protein Kinases
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MTOR protein, human
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinase Kinases
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AICA ribonucleotide
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Sirolimus