Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.

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Title Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.
Author Vider, Jelena
Journal Name Cancer Research
Year Published 2004
Place of publication United States of America
Publisher American Association for Cancer Research
Abstract Tumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor and host tissue-specific processes. To study the dynamics and spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging of hypoxia-induced HIF-1 transcriptional activity in tumors in living mice. This approach uses a novel retroviral vector bearing a HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion) and a constitutively expressed "beacon" reporter gene (DsRed2/XPRT). C6 glioma cells transduced with this multireporter system revealed dose-dependent patterns in temporal dynamics of HIF-1 transcriptional activity induced by either CoCl2 or decreased atmospheric oxygen concentration. Multicellular spheroids of C6 reporter cells developed a hypoxic core when >350 microm in diameter. 18F-2'-fluoro-2'deoxy-1beta-D-arabionofuranosyl-5-ethyl-uracil (FEAU) PET revealed spatial heterogeneity of HIF-1 transcriptional activity in reporter xenografts in mice as a function of size or ischemia-reperfusion injury. With increasing tumor diameter (>3 mm), a marked increase in HIF-1 transcriptional activity was observed in the core regions of tumors. Even a moderate ischemia-reperfusion injury in small C6 tumors caused a rapid induction of HIF-1 transcriptional activity, which persisted for a long time because of the inability of C6 tumors to rapidly compensate acute changes in tumor microcirculation.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1034/j.1600-0838.2002.120307.x
Volume 64
Issue Number 17
Page from 6101
Page to 6108
ISSN 0008-5742
Date Accessioned 2012-04-11; 2012-07-12T23:44:38Z
Date Available 2012-07-12T23:44:38Z
Research Centre Heart Foundation Research Centre; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Cancer Cell Biology
URI http://hdl.handle.net/10072/45851
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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