The analysis of centrosome replication cycle in Bowen's disease

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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.