Alteration of p53-binding protein 1 expression during skin carcinogenesis: association with genomic instability.
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概要
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The definitive version is available at www.blackwell-synergy.comEpidermal cells are the first cells to be exposed to environmental genotoxic agents such as ultraviolet (UV) and ionizing radiations (IR), which induce DNA double strand breaks (DSBs) and activate DNA damage response (DDR) to maintain genomic integrity. Defective DDR can result in genomic instability (GIN) which is considered to be a central aspect of any carcinogenic process. P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DSBs and rapidly form nuclear foci, the presence of 53BP1 nuclear foci can be considered as a cytological marker for endogenous DSBs reflecting GIN. The levels of GIN were analyzed by immunofluorescence studies of 53BP1 in 56 skin tumors that included 20 seborrheic keratosis (SK), 8 actinic keratosis (AK), 9 Bowen’s disease (BD), 9 squamous cell carcinoma (SCC), and 10 basal cell carcinoma (BCC). This study demonstrated a number of nuclear 53BP1 foci in human skin tumorigenesis, suggesting a constitutive activation of DDR in skin cancer cells. Because AK showed a high DDR type of 53BP1 immunoreactivity, GIN seems to be induced at the precancerous stage. Furthermore, invasive cancers exhibited a high level of intense, abnormal 53BP1 nuclear staining with nuclear accumulation of p53, suggesting a disruption of DDR leading to a high level of GIN in cancer cells. The results of this study suggest that GIN has a crucial role in the progression of skin carcinogenesis. The detection of 53BP1 expression by immunofluorescence can be a useful histological marker to estimate the malignant potential of human skin tumors.
- 2008-05-10
著者
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NARUKE Yuki
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Scie
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NAKASHIMA Masahiro
Tissue and Histopathology Section, Division of Scientific Data Registry, Nagasaki University Graduat
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SUZUKI Keiji
Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences
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MATSUU MATSUYAMA
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Scie
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SHICHIJO Kazuko
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Scie
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KONDO Hisayoshi
Biostatics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki Un
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SEKINE Ichiro
Tissue and Histopathology Section, Division of Scientific Data Registry, Nagasaki University Graduat
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Sekine I
Tissue And Histopathology Section Division Of Scientific Data Registry Atomic Bomb Disease Institute
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Sekine Ichiro
長崎大学 医歯薬学総合研究科腫瘍診断病理学
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MATSUU-MATSUYAMA Mutsumi
Department of Tumor and Diagnostic Pathology, Nagasaki University Graduate School of Biomedical Scie
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Shichijo Kazuko
Department Of Tumor And Diagnostic Pathology Nagasaki University Graduate School Of Biomedical Scien
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Kondo Hisayoshi
Biostatistics Section Division Of Scientific Data Registry Atomic Bomb Disease Institute Nagasaki Un
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Nakashima Masahiro
Tissue And Histopathology Section Division Of Scientific Data Registry Atomic Bomb Disease Institute
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Nakashima Masahiko
Tissue And Histopathology Section Division Of Scientific Data Registry Atomic Bomb Disease Institute
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Nakashima Masahiro
長崎大医歯薬学総合研究科原研 病態分子解析
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Nakashima Masahiro
Tissue And Histopathology Section Division Of Scientific Data Registry Nagasaki University Graduate
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Matsuu Mutsumi
Department Of Tumor And Diagnostic Pathology Nagasaki University Graduate School Of Biomedical Scien
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Shichijo Kazuko
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 病理
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Sekine Ichiro
Tissue And Histopathology Section Division Of Scientific Data Registry Atomic Bomb Disease Institute
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Sekine Ichiro
長崎大学医学部附属原爆後障害医療研究施設 生体材料保存室
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Naruke Yuki
Department Of Tumor And Diagnostic Pathology Nagasaki University Graduate School Of Biomedical Scien
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Sekine Ichiro
Div. Of Tumor And Diagnostic Pathology Atomic Bomb Disease Inst. Nagasaki Univ. Graduate School Of B
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Sekine Ichiro
Department Of Pathology Atomic Disease Institute Nagasaki University School Of Medicine
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Sekine Ichiro
Division Of Tumor And Diagnostic Pathology Atomic Disease Institute Nagasaki University Graduate Sch
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Shichijo Kazuko
Department Of Tumor And Diagnostic Pathology Atomic Bomb Disease Institute
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Sekine Ichiro
Tissue And Histopathology Section Division Of Scientific Data Registry Nagasaki University Graduate
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Sekine Ichiro
Department Of Molecular Pathology Atomic Bomb Disease Institute Nagaski University School Of Medicin
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Suzuki Keiji
Department Of Electrical Engineering Nagoya University
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Naruke Yuki
Department Of Pathology National Nagasaki Medical Center
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Shichijo Kazuko
Department of Pathology Atomic Disease Institute, Nagasaki University School of Medicine
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