研究発表を行った学会；2004 (95th) American Association for Cancer Researth (AACR) Annual Meeting ２００４年３月２７日〜３１日（Orlando, Florida, US）
タイトル；Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary gland of mouse model
発表者；張　東威　氏
　　　（熊本大学　医学薬学研究部　腫瘍医学分野）
Abstract；
Aurora-A, a serine-threonine mitotic kinase, was reported to be overexpressed in various human cancers and induce aneuploidy, centrosome amplification and tumorigenic transformation in human and rodent cells. However, the role of Aurora-A in tumorigenesis and malignant progression is largely unknown. Here we created a transgenic mouse model to investigate the involvement of Aurora-A overexpression in development of mammary glands and tumorigenesis using a Cre-loxP system. The conditional expression of Aurora-A resulted in significantly increased binucleated cell formation and apoptosis in the mammary epithelium. The levels of p53 protein were remarkably increased in these tissues. The surviving mammary epithelial cells composed hyperplastic areas after a short latency. Induction of Aurora-A overexpression in mouse embryonic fibroblasts also resulted in aberrant mitosis and binucleated cells followed by apoptosis. The apoptosis in MEFs was reversed by pifithrin-_, a specific p53 inhibitor, suggesting that p53 is responsible for the increased apoptosis induced by Aurora-A overexpression. Our findings indicate that this mouse model is a useful system for studying physiological roles of Aurora-A and genetic pathways of the Aurora-A-induced carcinogenesis.