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Genetic Determinants That Influence Hypoxia‐Induced Apoptosis

2001; Wiley; Linguagem: Inglês

10.1002/0470868716.ch8

1935-4657

Rodolfo Alarcón, Nicholas Denko, Amato J. Giaccia,

interferon and immune responses

Genetic Determinants That Influence Hypoxia-Induced Apoptosis Rodolfo M. Alarcon, Rodolfo M. Alarcon Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this authorNicholas C. Denko, Nicholas C. Denko Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this authorAmato J. Giaccia, Corresponding Author Amato J. Giaccia Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USAStanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this author Rodolfo M. Alarcon, Rodolfo M. Alarcon Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this authorNicholas C. Denko, Nicholas C. Denko Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this authorAmato J. Giaccia, Corresponding Author Amato J. Giaccia Stanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USAStanford University School of Medicine, Department of Radiation Oncology, Division of Radiation & Cancer Biology, CCSR-South, Rm. 1255, 269 Campus Drive, Stanford, CA 94305-5152, USASearch for more papers by this author Book Editor(s):Jamie A. Goode, Jamie A. GoodeSearch for more papers by this authorDerek J. Chadwick, Derek J. Chadwick OrganizerSearch for more papers by this author First published: 19 February 2001 https://doi.org/10.1002/0470868716.ch8Citations: 10Book Series:Novartis Foundation Symposia Series Editor(s): Novartis Foundation, Novartis FoundationSearch for more papers by this author AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Summary The p53 tumour suppressor gene is capable of activating both death receptor and mitochondrial-signalled forms of apoptotic cell death in response to diverse stimuli. Studies have suggested that impairment of the mitochondrial-signalled Apaf/caspase 9 pathway and not the death receptor Fas pathway results in almost complete resistance to apoptotic cell death induced by a low oxygen environment. However, it is unclear how p53 signals the activation of this pathway and whether it is through already identified p53 effector genes such as the pro-apoptotic gene bax, or through novel effectors such as BNIP-3/BNIP-3L. Comparison of cell lines genetically matched at the bax, cytochrome c, apaf, caspase 9 and caspase 3 loci indicated that except for bax, all of these genes were essential for hypoxia induced apoptosis both in cell culture and in transplanted tumours. These data imply that cytochrome c plays a pivotal role in signalling cell death by apoptosis under hypoxic conditions, and that the release of cytochrome c is independent of both Bax and p53. In contrast to cytochrome c, p53 modulates the magnitude of apoptosis under hypoxic conditions, but in itself is not required for the activation of the caspase cascade. Citing Literature The Tumour Microenvironment: Causes and Consequences of Hypoxia and Acidity: Novartis Foundation Symposium 240, Volume 240 RelatedInformation