Identification of trans-differentiation origin signals and their application to fertility-preservation therapy in young endometrial carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20781
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kitasato University
• Principal Investigator: Yokoi Ako 北里大学, 医学部, 助教 (90907148)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 子宮内膜癌 / morule / PTEN過剰発現 / EBP50 / β-カテニン

Outline of Final Research Achievements

Since PTEN was highly expressed in morules, PTEN-overexpressing cell lines were generated, which showed increased expression of Slug and decreased expression of E-cadherin, and morphological changes toward fibroblast-like cells, suggesting EMT. Moreover, the proliferative activity was decreased and the number of senescence cells increased. In addition, the increased expression of ALDH1 and CD44s suggested that PTEN overexpression gains CSC-like features. A possible factor was Cyclin D2, which is thought to be involved in the control of undifferentiated cell cycle and proliferation, and may be regulated via β-catenin. Part of the molecular mechanism of trans-differentiation was elucidated.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

本研究は、若年子宮内膜癌患者の妊孕性温存を目的とするMPA治療法の改良・確立を目指すことで、基礎研究と臨床研究の橋渡し的位置づけとなる。これは、臨床検体の詳細な解析結果と培養細胞を用いた関連分子の機能解析結果をハイブリッドすることにより、本治療法の分子基盤の一側面の解明が可能となる。最終的に、得られた成果を実臨床現場にフィードバックして、挙児希望の若年子宮内膜癌患者に対するMPA治療法の有益な効果判定や予後予測システムの構築を目指す。