アクティブボード・２０１５年１１月
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研究発表を行った学会；
・第７４回 日本癌学会学術総会
　２０１５年１０月　８日〜１０日（名古屋）
タイトル；The polymorphism in codon 389 of PICT-1 is associated with regulation of p53 stabilization.
発表者；吉本　賢史　氏
　　　（熊本大学　大学院生命科学研究部　構造機能解析学分野）
要旨；
The PICT-1 has tumor suppressor functions, but its precise function in uterine cancer has been unclear. To investigate the association of PICT-1 abnormalities with uterine cancers, firstly we found missense mutations of functionally important regions of PICT-1 in two of 13 uterine cancer cell lines and one of 20 surgical samples. Next, we examined codon 389 polymorphism in 124 cancer samples. There was a statistically significant increase in the risk of uterine cervical cancers associated with A/G (odds ratio 6.48, 95% confidence interval1.98-21.22, P = 0.0012), G/G (odds ratio 3.15, 95% confidence interval 1.03-9.61, P = 0.0403), and A/G or G/G (odds ratio 4.44, 95% confidence interval 1.62-12.23, P = 0.0026). For endometrial cancers, there was a statistically significant increase in risk associated with A/G (odds ratio 6.21, 95% confidence interval 1.84-20.99, P = 0.0021) and A/G or G/G (odds ratio 3.92, 95% confidence interval 1.38-11.16, P = 0.008). Furthermore, the overexpression of wild type PICT-1 induced the inhibition of exo-/endogenous p53 degradation in presence or absence HPV18 E6, while codon 389 polymorphic type of PICT-1 slightly had this inhibitory effect to p53 degradation as compared to wild type PICT-1. In addition, we identified PICT-1 expression was reduced in uterine cancer cell lines and uterine cancer tissues. Our results indicate that disruption of PICT-1 by gene mutation and/or reduction of protein level may associate with the pathogenesis of human uterine cancers, and its codon 389 polymorphism may increase the risk of uterine cancers throughout the impairment of the inhibitory of p53 degradation by PICT-1.