Potential role of the Mieap-regulated mitochondrial quality control in murine intestinal tumorigenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Nakamura Yasuyuki 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (90569063)
• Co-Investigator(Renkei-kenkyūsha): ARAKAWA HIROFUMI 国立研究開発法人国立がん研究センター, 研究所, 分野長 (70313088) ; KAMINO HIROKI 国立研究開発法人国立がん研究センター, 研究所, 研究員 (00625692)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: p53 / ミトコンドリア / ROS / 腫瘍抑制 / がん / ApcMin/+マウス

Outline of Final Research Achievements

Mieap, a novel p53-inducible protein, plays a key role in maintaining healthy mitochondria in various pathophysiological states. To understand the role that Mieap plays in in vivo tumorigenesis, we generated Mieap-deficient ApcMin/+ mice. The Mieap-deficient ApcMin/+ mice revealed remarkable shortening of the lifetime compared to ApcMin/+ mice. A substantial increase in the number and size of intestinal polyps was associated with Mieap gene deficiency. Histopathologically, intestinal tumors in the Mieap-deficient ApcMin/+ mice clearly demonstrated advanced grades of adenomas and adenocarcinomas. We demonstrated that the significant increase in morphologically unhealthy mitochondria and trace accumulations of ROS may be mechanisms underlying the increased malignant progression of the intestinal tumors of Mieap-deficient ApcMin/+ mice. These findings suggest that the Mieap-regulated mitochondrial quality control plays a critical role in preventing mouse intestinal tumorigenesis.

Free Research Field

腫瘍生物学