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

被引：27

作者：

Borger, Darrell R. ^{[2
]}

Gavrilescu, L. Cristina ^{[1
]}

Bucur, Maria C. ^{[1
]}

Ivan, Mircea ^{[1
]}

DeCaprio, James A. ^{[2
]}

机构：

[1] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 02期

关键词：

hypoxia; AMPK; mTOR; rapamycin; apoptosis; cancer;

D O I：

10.1016/j.bbrc.2008.03.056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：230 / 234

页数：5

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