Functional analysis of AMBRA1 a new candidate of Cowden syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16755
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tokai University
• Principal Investigator: Akatsuka Hisako 東海大学, 医学部, 特定研究員 (20826317)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: AMBRA1 / 細胞増殖 / 腫瘍

Outline of Final Research Achievements

We detected "AMBRA1" as a new candidate gene of Cowden syndrome. Patient AMBRA1 had amino acid change which was conceived as cause functional severe defect. Actually, patient AMBRA1 was dysfunction. So far, AMBRA1 had not been analyzed in physiological condition, we made Ambra1 conditional Knock Out mice (here in Ambra1 cKO mice). The organ size of this mice is larger than that of the control mice, which is considered to be an dysregulation of cell proliferation. And tumor sensitivity were high. In addition, abnormaly proliferation and infiltration of myeloid cell was detected in liver and lung of Ambra1 cKO mice. Therefore we uncovered that AMBRA1 suppresses tumor and regulates blood cell differentiation correctly.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では世界で初めてヒトの生殖系細胞にAMBRA1遺伝子の変異を見出し、かつ機能欠失型であることを明らかにした。また、AMBRA1が腫瘍抑制遺伝子として機能することを生理的な実験系で証明できた。家族性腫瘍は稀な疾患であるが、そのほとんどが腫瘍抑制遺伝子の変異による。家族性腫瘍の原因遺伝子の解析によって、生命の理解に重要な知見が重ねられてきた。Cowden症候群も同様に稀な家族性腫瘍であるが、AMBRA1の解析によって生命の新たな知見を得ることができた。