Induction of stem cell features by S100A4/NMII signals in uterine carcinosarcoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kitasato University
• Principal Investigator: Saegusa Makoto 北里大学, 医学部, 教授 (00265711)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: S100A1 / p53 / MDM2 / 子宮内膜癌

Outline of Final Research Achievements

S100A1 interacted with MDM2 but not p53 in endometrial cancer (Em Ca) cell lines. Treatment of cells stably overexpressing S100A1 with Nutlin-3A, an inhibitor of the p53/MDM2 interaction, increased expression of p53-target genes including p21waf1 and BAX. S100A1 overexpression enhanced cellular migration, but also sensitized cells to the antiproliferative and proapoptotic effects of Adriamycin, a genotoxic agent; these phenotypes were abrogated when S100A1 was knocked down using shRNA. In clinical samples from normal endometrium, S100A1 expression was significantly higher in endometrial glandular cells of the middle/late secretory and menstrual stages when compared to cells in the proliferative phases; high S100A1 was also positively correlated with expression of MDM2 and p21waf1 and apoptotic status, and inversely correlated with Ki-67 scores. However, such correlations were absent in Em Ca tissues.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、コロナ渦による研究環境の変化等に計画通りに進めることが困難となった。そこで、子宮がん肉腫の起源である子宮内膜癌を対象に、まずは、S100ファミリーメンバーが子宮内膜腺細胞の恒常性維持や発がんに関与する可能性について、S100A1とp53/MDM2との関連した結果、S100A1 の発現は、正常子宮内膜組織の月経周期において、MDM2 との相互作用を通じて細胞増殖、アポトーシス、移動を調節している。一方、子宮内膜癌では、このような機能相関が破綻していることを明らかした。この研究成果は、子宮がん肉腫発生過程におけるS100ファミリーの機能を解明の第一段階で、今後は当初の研究目的を検証する。