Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-4-1
pubmed:abstractText
Hypoxia-inducible factor-1 (HIF-1) is responsible for various gene expressions related to tumor malignancy, such as metastasis, invasion and angiogenesis. Therefore, monitoring HIF-1 activity in solid tumors is becoming increasingly important in clinical and basic studies. To establish a convenient system for visualizing HIF-1 activity in tumor xenografts, we employed a promoter consisting of five copies of hypoxia response elements (5HRE), whose activity depends on HIF-1, and used a derivative of green fluorescence protein (d2EGFP) as a reporter gene. A human melanoma cell line, Be11, which contains the 5HRE-d2EGFP gene, showed fluorescence in response to hypoxia. The fluorescent intensity correlated inversely with the surrounding oxygen tension, and was time-dependent for the hypoxic treatment. Reoxygenation resulted in a rapid decrease in fluorescence due to the signal sequence for protein degradation encoded in d2EGFP, which enabled monitoring of HIF-1 activity in real-time. Heterogeneous fluorescence was observed in the solid tumor of a non-sacrificed tumor-bearing mouse. Immunohistochemical analysis confirmed that d2EGFP-expressing regions overlapped with the ones stained with a hypoxia marker, pimonidazole. These results suggest that the 5HRE-d2EGFP gene is suitable for the real-time imaging of HIF-1-activating cells in vivo, due to the short half-life of the d2EGFP protein as well as the specificity of the 5HRE promoter for HIF-1 activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0449-3060
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-102
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Real-time imaging of hypoxia-inducible factor-1 activity in tumor xenografts.
pubmed:affiliation
Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies