Real-time Imaging of Hypoxia-inducible Factor-1 Activity in Tumor Xenografts
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概要
- 論文の詳細を見る
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, Bell, 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.
- 日本放射線影響学会の論文
- 2005-03-25
著者
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HARADA Hiroshi
Department of Pathology, Kurume University School of Medicine
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SHIBATA Toru
Department of Radiology, Faculty of Medicine, Kyoto University
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HIRAOKA Masahiro
Department of Radilogy and Nuclear Medicine, Faculty of Medicine, Kyoto University
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OGURA Masakazu
Department of Therapeutic Radiology and Oncology, Graduate School of Medicine, Kyoto University
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QU Runjiang
Department of Neurology, Henry Ford Health System
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Qu Runjiang
Department Of Therapeutic Radiology And Oncology Kyoto University Graduate School Of Medicine:depart
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Qu Runjiang
Department Of Neurology Henry Ford Health System
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Hiraoka Masahiro
Department Of Radiology Kyoto University Hospital
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Hiraoka Masahiro
京都大学医学部附属病院 呼吸器外科
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Hiraoka Masahiro
Department Of Therapeutic Radiology And Oncology Kyoto University Graduate School Of Medicine
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LIU Junye
Department of Therapeutic Radiology and Oncology, Kyoto University Graduate School of Medicine
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Hiraoka Masahiro
Department Of Pediatrics Fukui Medical School
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Shibata Toru
Department Of Therapeutic Radiology And Oncology Kyoto University Graduate School Of Medicine
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Shibata Toru
Department Of Physics Aoyama Gakuin University
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Ogura Masakazu
Department Of Therapeutic Radiology And Oncology Kyoto University Graduate School Of Medicine
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Ogura Masakazu
Department Of Therapeutic Radiology And Oncology Graduate School Of Medicine Kyoto University
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Liu Junye
Department Of Therapeutic Radiology And Oncology Kyoto University Graduate School Of Medicine:depart
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Shibata T
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:horizo
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Harada Hiroshi
Department Of Electrical Engineering Osaka University
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Hiraoka Masahiro
Department Of Radiation Oncology And Image-applied Therapy Kyoto University Graduate School Of Medic
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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 Anatomy, Kurume University School of Medicine
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OGURA Masakazu
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine
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