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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1876-1882.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-1859.
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NEOPLASIA
Anoxic induction of ATF-4 through HIF-1–independent pathways of protein stabilization in human cancer cells
Kurosh Ameri,
Claire E. Lewis,
Martin Raida,
Heidi Sowter,
Tsonwin Hai, and
Adrian L. Harris
From Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; the Division of Genomic Medicine, Section of Oncology, Sheffield Medical School, Sheffield, United Kingdom; and the Department of Molecular and Cellular Biochemistry, Neurobiotechnology Center, Ohio State University, Columbus.
Hypoxia is a key factor in tumor development, contributing to angiogenesis and radiotherapy resistance. Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor regulating the response of cancer cells to hypoxia. However, tumors also contain areas of more severe oxygen depletion, or anoxia. Mechanisms for survival under anoxia are HIF-1 independent in Caenorhabditis elegans and, thus, differ from the hypoxic response. Here we report a differential response of cancer cells to hypoxia and anoxia by demonstrating the induction of activating transcription factor-4 (ATF-4) and growth arrest DNA damage 153 (GADD153) protein specifically in anoxia and the lack of induction in hypoxia. By applying RNAi, ATF-4 induction in anoxia was shown to be independent of HIF-1, and desferrioxamine mesylate (DFO) and cobalt chloride induced HIF-1 but not ATF-4 or GADD153. Furthermore, the inductive response of ATF-4 and GADD153 was not related to alterations in or arrest of mitochondrial respiration and was independent of von Hippel-Lindau (VHL) disease mutations. In reoxygenated anoxic cells, ATF-4 had a half-life of less than 5 minutes; adding the proteasome inhibitor to normoxic cells up-regulated ATF-4 protein. Extracts from primary human tumors demonstrated more ATF-4 expression in tumors near necrotic areas. Thus, this study demonstrates a novel HIF-1–independent anoxic mechanism that regulates ATF-4 induction at the protein stability level in tumor cells.
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|
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|
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|
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