The analysis of centrosome replication cycle in Bowen's disease

Bowen病中心体复制周期分析

• 批准号: 20591330
• 负责人: KUBO Akiharu
• 金额: $ 2.16万
• 依托单位: Keio 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 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591330/
• 关键词: 扁平上皮癌; Bowen病; 中心体; Aurora A kinase; aurora A kinase

Centrosome consists of mother and daughter centrioles and pericentriolar materials. Centrosome duplicates only once per cell cycle and the duplication cycle is strictly regulated. In many cancer cells, the centrosomal cycle is dysregulated, which induces multi-polar spindles or cytokinesis failure and aneuploidy. In this study, we established a specific antibody against daughter centrioles and succeeded to count the number of mother and daughter centrioles per cell in the biopsy specimens of Bowen's disease and squamous cell carcinoma. Centrosome duplication cycle was dysregulated and multiple centrioles were observed in so-called "clumping cells" of Bowen's disease. In clumping cells, the number of mother and daughter centrioles are almost same, which indicated that cytokinesis failure causes the formation of "clumping cells". We found that Aurora-A kinase was overexpressed in "clumping cells". So we established transgenic mice that overexpress Aurora-A kinase specifically in the epidermis. In these mice, binuclear cells were found in the basal layer of epidermis, suggesting that Aurora-A overexpression is associated with the pathogenesis of Bowen's disease.

中心体由母中心粒、子中心粒和中心粒周围物质组成。中心体在每个细胞周期中仅复制一次，并且复制周期受到严格的调控。在许多癌细胞中，中心体周期失调，从而诱导多极纺锤体或胞质分裂失败和非整倍体。本研究建立了一种抗女儿中心粒的特异性抗体，并成功地对Bowen病和鳞状细胞癌活检标本中每个细胞的母子中心粒数进行了计数。Bowen病的中心体复制周期失调，在所谓的“团块细胞”中观察到多个中心粒。在团块细胞中，母中心粒和子中心粒的数量几乎相同，这表明胞质分裂失败导致了“团块细胞”的形成。我们发现Aurora-A激酶在“凝集细胞”中过表达。因此，我们建立了在表皮特异性过表达Aurora-A激酶的转基因小鼠。在这些小鼠中，在表皮基底层中发现双核细胞，表明Aurora-A过表达与Bowen病的发病机制有关。

项目成果

Bowen病における中心体制御異常の検討

Bowen 病中心体失调的检查

• 发表时间: 2009
• 作者: Tsuchimoto;T.;Sakata;K.;Matsumoto;Y.;他(8名中6番目);久保亮治
• 通讯作者: 久保亮治

Identification of novel ciliary proteins using microarray analyses of in vitro ciliogenesis

利用体外纤毛发生的微阵列分析鉴定新型纤毛蛋白

• 发表时间: 2008
• 作者: A. Kubo;A. Yuba-Kubo;Sa. Tsukita;Sh Tsukita;M. Amagai
• 通讯作者: M. Amagai

External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers.

• DOI: 10.1084/jem.20091527
• 发表时间: 2009-12-21
• 期刊: The Journal of experimental medicine
• 作者: Kubo A;Nagao K;Yokouchi M;Sasaki H;Amagai M
• 通讯作者: Amagai M

Periungual squamous cell carcinoma induced by human papillomavirus type 59 in an immunosuppressed patient

免疫抑制患者由 59 型人乳头瘤病毒诱导的甲周鳞状细胞癌

• 发表时间: 2009
• 期刊: J. Am. Acad. Dermatol 61
• 作者: Tanese K;Akiyoshi A;Saito M;Kubo A;Takanashi M;Ishiko A
• 通讯作者: Ishiko A

Sentan: A Novel Specific Component of the Apical Structure of Vertebrate Motile Cilia

• DOI: 10.1091/mbc.e08-07-0691
• 发表时间: 2008-12-01
• 期刊: MOLECULAR BIOLOGY OF THE CELL
• 影响因子: 3.3
• 作者: Kubo, Akiharu;Yuba-Kubo, Akiko;Amagai, Masayuki
• 通讯作者: Amagai, Masayuki