A Novel Role for Thyroid Hormone Receptor Beta in Cellular Radiosensitivity
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概要
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長崎大学学位論文 学位記番号:博（医歯薬）甲第148号 博士（医学）学位授与年月日:平成20年3月19日Thyroid hormone receptors (THRs) widely govern cell growth, differentiation and metabolism acting in a ligand- and cofactor-dependent manner to modulate tissue-specific gene expression. Given a large variety of genes regulated by THRs and multiplicity of cellular processes potentially influenced by THRs, we addressed the role of THRB (thyroid hormone receptor beta) in cellular radiosensitivity. Wild-type and mutant THRB were overexpressed in several cell lines using an adenovirus-mediated gene delivery and their effects were examined after cell exposure to γ-rays. Wild-type THRB decreased clonogenic survival of the cell lines with low levels of endogenous THRB, retarded their growth and synergized with radiation in decreasing proliferative potential and promoting cellular senescence. These changes were accompanied by the accumulation of p21 (CDKN1A, CIP1, WAF1) and p16 (CDKN2A, INK4a) inhibitors of cyclindependent kinases and by the decrease of Rb (retinoblastoma protein) phosphorylation. Mutant THRB produced a radioprotective effect, attenuated radiation-induced growth inhibition and cellular senescence. The results suggest that THRB may modulate cellular radiosensitivity and stress-induced senescence.
- 日本放射線影響学会の論文
- 2008-01-15
著者
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Matsuse Michiko
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Matsuse Michiko
Graduate School Of Biomedical Sciences Nagasaki Univ.
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Mitsutake Norisato
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Mitsutake Norisato
長崎大学大学院医歯薬学総合研究科附属原爆後障害医療研究施設 分子医療部門
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Saenko V
Department Of International Health And Radiation Research Atomic Bomb Disease Institute Nagasaki Uni
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Saenko Vladimir
長崎大学大学院医歯薬学総合研究科附属原爆後障害医療研究施設 分子医療部門分子診断研究分野
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Saenko Vladimir
長崎大学 医歯薬学総合研究科展開医療科学講座形成再建外科学
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Yamashita S
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Yamashita S
Department Of Molecular Medicine Nagasaki University School Of Medicine
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Yamashita S
Radiation And Environmental Health Department Of Protection Of The Human Environment World Health Or
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NAMBA Hiroyuki
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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ROGOUNOVITCH Tatiana
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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NAKAZAWA Yuka
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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YAMASHITA Shunichi
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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Saenko Vladimir
Department Of International Health And Radiation Research Atomic Bomb Disease Institute Nagasaki Uni
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Namba Hiroyuki
Department Of Molecular Medicine Nagasaki University Graduate School Of Biomedical Sciences
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Nakazawa Yuka
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Yamashita Shunichi
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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SEDLIAROU Ilya
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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AKULEVICH Natallia
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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Shibata Yoshisada
長崎大学医学部附属原爆後障害医療研究施設 放射線疫学 研究分野
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Shibata Yoshisada
Atomic Bomb Disease Institute Nagasaki Univ. Graduate Sch. Biomedical Sciences
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Namba Hiroyuki
Department Of Cell Physoloy Atomin Disease Institute Nagasaki University School Of Medicint
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Sedliarou Ilya
Department Of Molecular Medicine Nagasaki University Graduate School Of Biomedical Sciences
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Yamashita Shunichi
Dep. Of Molecular Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences
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Shibata Yoshisada
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Saenko Vladimir
Department Of International Health And Radiation Research Atomic Bomb Disease Inst. Nagasaki Univ. S
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Rogounovitch Tatiana
Department Of Molecular Medicine Atomic Bomb Disease Institute Nagasaki University Graduate School O
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Rogounovitch Tatiana
Department Of Nature Medicine Atomic Bomb Disease Inst. Nagasaki Univ. Sch. Med.
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Yamashita Shunichi
Department Of Cell Physiology Atomic Disease Institute Nagasaki University School Of Medicine
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Shibata Yosisada
Rerf
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Saenko Vladimir
Department Of Health Risk Control Nagasaki University Graduate School Of Biomedical Sciences
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Mitsytake Norisato
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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