AMP-activated protein kinase is essential for survival in chronic hypoxia
Copyright policy )AMP-activated protein kinase is essential for survival in chronic hypoxia
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.
- Harvard University United States
- Molecular Research Institute United States
- Tufts Medical Center United States
- Dana-Farber Cancer Institute United States
Sirolimus, Cell Survival, TOR Serine-Threonine Kinases, Ribonucleotides, Aminoimidazole Carboxamide, Cell Hypoxia, AMP-Activated Protein Kinase Kinases, Cell Line, Tumor, Humans, Protein Kinase Inhibitors, Protein Kinases, Cell Line, Transformed
Sirolimus, Cell Survival, TOR Serine-Threonine Kinases, Ribonucleotides, Aminoimidazole Carboxamide, Cell Hypoxia, AMP-Activated Protein Kinase Kinases, Cell Line, Tumor, Humans, Protein Kinase Inhibitors, Protein Kinases, Cell Line, Transformed
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