The analysis of centrosome replication cycle in 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。

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.