The significance of 53BP1 nuclear foci as a universal tumor tissue marker

53BP1核灶作为通用肿瘤组织标志物的意义

• 批准号: 20590367
• 负责人: NAKASHIMA Masahiro
• 金额: $ 3万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590367/
• 关键词: 癌; 53BP1; ゲノム不安定性; 蛍光免疫染色; 53BP

The presence of sporadic DNA double strand breaks (DSBs) is considered as a characteristic feature of genomic instability (GIN). It has been proposed that GIN has a crucial role during several carcinogenesis, and is associated with malignant potential of neoplasms. The presence of 53BP1 nuclear foci (NF) can be a cytologic marker for endogenous DSBs reflecting GIN. This study analyzed the level of GIN, as detected with immunofluorescence of 53BP1 expression, in a variety of resected tumors to evaluate the significance of 53BP1 expression as a universal tumor tissue marker. In results : 1) a number of 53BP1NF and abnormal type of 53BP1 expression were demonstrated in thyroid cancers, suggesting a high level of GIN ; 2) during skin carcinogenesis, GIN seems to be induced at the precancerous stage with constitutive activation of DNA damage response (DDR). Furthermore, invasive cancers exhibited abnormal 53BP1 staining, reflecting a disruption of DDR; 3) The number of 53BP1NF in uterine cervical cells appeared to increase with progression during carcinogenesis and to be significantly associated with the expression of human papilloma virus (HPV) signals.

散发性DNA双链断裂（DSBs）的存在被认为是基因组不稳定性（GIN）的特征。已有研究表明，GIN在多种肿瘤发生过程中起着至关重要的作用，并与肿瘤的恶性潜能有关。53BP1核病灶（NF）的存在可以作为内源性DSBs反映GIN的细胞学标志物。本研究通过免疫荧光法检测53BP1的表达，分析GIN在多种切除肿瘤中的表达水平，以评价53BP1表达作为一种通用的肿瘤组织标志物的意义。结果：1)甲状腺癌中53BP1NF表达较多，53BP1表达类型异常，提示GIN水平较高；2)在皮肤癌发生过程中，GIN似乎是在癌前阶段通过DNA损伤反应（DDR）的组成性激活而诱导的。此外，浸润性癌症表现出异常的53BP1染色，反映了DDR的破坏；3)宫颈细胞中53BP1NF的数量随着癌变过程的进展而增加，并与人乳头瘤病毒（HPV）信号的表达显著相关。

项目成果

Foci formation of P53-binding protein 1 in thyroid tumors: Activation of genomic instability during thyroid carcinogenesis

• DOI: 10.1002/ijc.23223
• 发表时间: 2008-03-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Nakashima, Masahiro;Suzuki, Keiji;Sekine, Ichiro
• 通讯作者: Sekine, Ichiro

Mutational screening of the BRCA1 gene in sporadic breast cancer in Kazakhstan population.

哈萨克斯坦人群散发性乳腺癌 BRCA1 基因突变筛查。

• 发表时间: 2011
• 期刊: Breast J
• 影响因子: 2.1
• 作者: Kojima Y;Akimoto K;Nagashima Y;Ishiguro H;Kobayashi N;Matsuzaki O;Shirai S;Aoki I;Yao M;Shima H;Akilzhanova A
• 通讯作者: Akilzhanova A

原爆症に関する調査研究分担報告書 共同研究課題2:原爆被爆者の免疫機能に関する研究成熟甲状腺濾胞上皮での放射線感受性と晩発性ゲノム不安定性解析

原子弹疾病联合研究报告 合作研究课题2：原子弹幸存者免疫功能研究 成熟甲状腺滤泡上皮放射敏感性和迟发型基因组不稳定性分析

• 发表时间: 2010
• 期刊: 平成21年度厚生労働省委託事業原爆症調査研究事業報告書
• 作者: S. Mitomo;C. Maesawa;S. Ogasawara;T. Iwaya;M. Shibazaki;A. Yashima-Abo;K. Kotani;H. Oikawa;E. Sakurai;N. Izutsu;K. Kato;H. Komatsu;K. Ikeda;G. Wakabayashi;T. Masuda;中島正洋
• 通讯作者: 中島正洋

Living-donor liver transplantation from second generation children for atomic bomb survivors

为原子弹幸存者进行第二代儿童活体肝移植

• 发表时间: 2009
• 期刊: Hepatol Res 39
• 作者: Yamaguchi J;et al.;Motosugi U.;Eguchi S
• 通讯作者: Eguchi S

Acute DNA damage response and late carcinogenesis in rat thyroid glands after external irradiation

大鼠甲状腺外照射后的急性DNA损伤反应和晚期癌变

• 发表时间: 2010
• 作者: Takata;K.;Sato;Y.;Nakamura;N.;Kondo;E.;etal.;長嶋洋治;堀江良一;中島正洋
• 通讯作者: 中島正洋