Influences of the p53 Status on Hypoxia-induced Gene Expression
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概要
- 論文の詳細を見る
The p53 tumor-suppressor gene is one of the most frequently mutated genes in human cancers, and its genetic alterations may play critical roles in oncogenesis, tumor progression, and angiogenesis. To clarify the influence of the p53 status on hypoxia-inducible gene expression, we first performed transfection assays with a hypoxia-responsive vector carrying 5 hypoxia-responsive elements upstream of the human CMV minimal promoter driving transcription of the luciferase gene in various human tumor cell lines with wild-type (wt) or mutant (mut) p53. As a result, hypoxia responsiveness considerably varied between cell lines, and we could not obtain clear evidence that the hypoxia-inducible factor-1 (HIF-1) mediated gene expression in the wt-p53 cells was lower than that in cells with mut-p53. It is interesting that SaOS2 cells (p53 null) showed the highest luciferase activities under both aerobic and hypoxic conditions among tested cells. Next, to elucidate the effects of endogenous wt-and mut-p53s, a transfection assay and Northern blot analysis for VEGF transcription under hypoxia were performed by using isogenic variants of HT1080 cells differing in their p53 status. The luciferase and the endogenous VEGF mRNA expression were apparently lower in a variant carrying mutations in both p53 alleles than in a parental line harboring wt-p53, implying that some types of mutant p53 constitutively accumulated in cells can decrease both the basal and the hypoxia-induced expressions in addition to wt-p53.
- 日本放射線影響学会の論文
- 2004-06-15
著者
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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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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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OGURA Masakazu
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine
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