Elucidation of chromatin regulation and epithelial-mesenchymal transition regulatory mechanism by TSHZ2, a novel prognostic factor in breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16182
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Riku Miho 愛知医科大学, 医学部, 助教 (50762390)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 乳癌 / 核タンパク / 上皮間葉転換

Outline of Final Research Achievements

This study aims to analyze the function of a novel transcriptional repressor teashirt homolog 2 (TSHZ2) in breast cancer, clarify its clinical significance, and utilize it for pathological diagnosis. The TSHZ2 gene knockout cell line of normal mammary epithelial cell line established in this study showed morphological change to mesenchymal cell-like. We analyzed the underlying molecular mechanisms and revealed that the expression patterns of multiple isoforms of TSHZ2 differed between normal and cancer, which may be associated with malignant traits such as epithelial-mesenchymal transition. In the future, we will analyze the relationship between this expression pattern and clinicopathological features and aim to apply it as a surrogate marker for breast cancer.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、正常乳腺上皮細胞が癌化する過程において間葉系細胞様への形態および機能を獲得する際、癌抑制遺伝子のアイソフォーム発現パターンが変化するという新たな側面から知見を得た。この変化を定常状態に戻すことは癌細胞の生存にとって不都合であると推測され、乳癌の新規治療薬開発の糸口となる。また、このパターン変化を利用し、乳腺腫瘍の診断マーカーとして応用することもできる。アイソフォーム発現パターンを組織上で可視化し、パネリングすることで良悪性の判断に迷う早期乳癌の病理診断を行うためのツールとして提唱できる。