Real-time Imaging of Hypoxia-inducible Factor-1 Activity in Tumor Xenografts
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- LIU Junye
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine Department of Radiation Medicine, Fourth Military Medical University
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- QU Runjiang
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine Department of Radiation Medicine, Fourth Military Medical University
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- OGURA Masakazu
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine
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- SHIBATA Toru
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine
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- HARADA Hiroshi
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine Horizontal Medical Research Organization, Kyoto University Graduate School of Medicine
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- HIRAOKA Masahiro
- Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine
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抄録
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.<br>
収録刊行物
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- Journal of Radiation Research
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Journal of Radiation Research 46 (1), 93-102, 2005
Journal of Radiation Research 編集委員会
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詳細情報 詳細情報について
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- CRID
- 1390282680193497088
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- NII論文ID
- 110004041100
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- NII書誌ID
- AA00705792
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- ISSN
- 13499157
- 04493060
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- NDL書誌ID
- 7290604
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- PubMed
- 15802864
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- NDL-Digital
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可