Elucidation of the mrchanism of invasion in ductal carcinoma in situ

Research Project

Project/Area Number	18K16287
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Juntendo University
Principal Investigator	Horimoto Yoshiya 順天堂大学, 医学部, 准教授 (40424246)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	非浸潤性乳癌 / 浸潤 / 上皮間葉移行 / 転移 / HER2
Outline of Final Research Achievements	Using non-invasive breast cancer cell line, we found that EMT inhibitors suppressed cell migration and invasion. In vivo, suppression of the lung metastasis was confirmed. Employing surgical specimens, whether tumours with high expression of EMT markers more frequently had microinvasion and postoperative local recurrence rates were examined. In addition, we found that many exstrogen receptor-positive non-invasive breast cancers overexpressed HER2 protein without gene amplification. In the future, we hope that the inhibitory effect of EMT inhibitors will lead to a completely new treatment strategy for patients with non-invasive breast cancer without surgery.
Academic Significance and Societal Importance of the Research Achievements	エストロゲン受容体陽性HER2陽性非浸潤癌症例の多くがHER2/neu遺伝子増幅なしにHER2蛋白を過剰に発現していることを明らかにした。またin vivoの実験において、EMT阻害剤により肺転移が抑制されることを明らかにした。本研究の成果によりEMT阻害剤により浸潤癌への進行を食い止め、非浸潤癌を手術せずに治療するという全く新しい治療法を提案し、臨床試験立案のための重要なデータを構築したいと考えている。