Biochem Biophys Res Commun. 2008 May 30;370(2):230-4. Epub 2008 Mar 24.

AMP-activated protein kinase is essential for survival in chronic hypoxia.

Borger DR, Gavrilescu LC, Bucur MC, Ivan M, Decaprio JA.

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Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Mayer Building 440, 44 Binney Street, Boston, MA 02115, USA.

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.

PMID:: 18359290; [PubMed - indexed for MEDLINE]
PMCID:: PMC2387098

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