Hormone-dependent cancer and the transcriptional coactivator MED1

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15418
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kobe University
• Principal Investigator: HASEGAWA NATSUMI 神戸大学, 保健学研究科, 助教 (20708599)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 転写メディエーター / MED1 / 乳癌

Outline of Final Research Achievements

We have previously shown that Mediator subunit MED1 acts as a specific coactivator of ERα and is involved in the proliferation of pubertal mammary epithelial cells and ERα-positive breast cancer cells.
In order to determine the role for MED1 in the property of breast carcinomas, prognosis, response to therapy, and therapeutic resistance, we have prepared mouse models of mammary tumorigenesis harboring mutation of MED1. MED1 mutant mice lacking the nuclear receptor binding motifs had delayed tumor onset and changed localization of ERα. We proposed a new molecular mechanism by which the nuclear receptor-binding ability of MED1 contributes to growth of ERα-positive breast cancer cells.

Free Research Field

腫瘍検査学

Academic Significance and Societal Importance of the Research Achievements

乳癌の約80%はERαを発現し、タモキシフェン等の抗エストロゲン製剤は臨床で広く使用されているが、MED1はそのシグナル伝達を担うことから治療抵抗性にも関与する。本研究ではMED1がERαの核局在化を調節することにより、MED1の核内受容体結合能力がERα陽性乳癌細胞の増殖に関与する新しい分子メカニズムを提案した。本研究の先に、MED1を標的とする治療アプローチがありうることを示すものであり、今後の研究の動向に期待したい。