The molecular mechanisms of tamoxifen-resistance induction by intracellular amino acids in ER-positive breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07620
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Keio University
• Principal Investigator: SAITO Yasuhiro 慶應義塾大学, 政策・メディア研究科(藤沢), 特任准教授 (30613004)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 乳がん / アミノ酸トランスポーター / 薬剤耐性

Outline of Final Research Achievements

In this study, we analyzed the molecular mechanism of the acquisition of tamoxifen resistance in estrogen receptor-positive breast cancer, which accounts for the majority of breast cancers. We have previously focused on the amino acid transporter SLC7A5, whose function is specifically upregulated in ER-positive breast cancer cells. Since upregulation of SLC7A5 function is associated with the acquisition of tamoxifen resistance, we focused our analysis on the amino acids taken up by SLC7A5. We successfully identified the amino acid leading to the tamoxifen resistance. In this study, we succeeded in identifying the amino acids involved in the acquisition of tamoxifen resistance, and are now in the process of analyzing the molecular mechanism in detail.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果とその後の進展により、乳がんの大部分を占めるエストロジェン受容体陽性乳がん治療法に認められるホルモン療法耐性乳がんの新たな治療法開発に貢献することができると考えられることから社会的意義があるといえる。また、アミノ酸に認められる新たな生物学的役割を明らかにすることは学術的にも重要であるといえる。