Investigation of the significance of PPP2R1A mutation in endometrial carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Shinshu University
• Principal Investigator: FUSEYA Chiho 信州大学, 医学部附属病院, 助教(診療) (50447736)
• Co-Investigator(Kenkyū-buntansha): 井田 耕一 信州大学, 医学部附属病院, 助教(診療) (10773442) ; 宮本 強 信州大学, 学術研究院医学系, 准教授 (70418721)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: PIM1 / RPP2R1A / PP2A / 子宮内膜癌 / 子宮内膜漿液性癌 / リン酸化脱リン酸化

Outline of Final Research Achievements

PPP2R1A is a component of the PP2A complex, which dephosphorylates and represses oncogenes. PIM1 is an opposite factor of PP2A that phosphorylates target factors. We investigated the expression of PIM1 in endometrial carcinoma and found that PIM1 was strong in serous carcinoma (USC), with a significantly shorter overall survival in cases with high PIM1 expression. Suppression of PIM1 expression (PIM1-siRNA) reduced USC cell viability, migration, and invasion in vitro. Inhibition of PIM1 by PIM1 inhibitor (SGI-1776) also reduced cellular functions of USC cell lines. Oral administration with SGI-1776 significantly inhibited tumor growth in USC cell line ARK1 xenograft tumors transplanted subcutaneously in mice.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究成果はPPP2R1Aを含むPP2A複合体、および、それと拮抗的に作用するPIM1が子宮内膜癌の予後不良組織型である漿液性癌（SC）の悪性度上昇や予後に関連することを示した最初の報告であり、SCに対する新規治療につながる可能性がある意義を持つ。