Functional analysis of clock genes in invasive breast carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery; Human pathology
• Research Institution: Jichi Medical University (2019); Hirosaki University (2017-2018)
• Principal Investigator: Wu Yunyan 自治医科大学, 医学部, ポスト・ドクター (40636586)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 時計遺伝子 / がん微小環境 / 上皮間葉転換

Outline of Final Research Achievements

The present study declares the mechanisms that clock genes, DEC1 and DEC2, regulate the epithelial-mesenchymal transition (EMT) process.
First, DEC1 overexpression upregulated podoplanin expression in carcinoma cells whereas DEC2 overexpression inhibited podoplanin. Second, the expression of DEC1 was induced when exposed to hypoxic environment. Subsequently, DEC1 promoted the EMT process by inhibiting the expression of epithelial marker E-cadherin. Third, DEC1 and DEC2 functioned as regulators of the TGFβ-Smad signaling pathway to affect EMT process in carcinoma cells. Finally, we analyzed the morphological changes by observing under transmission electron microscope (TEM). Carcinoma cells were applied on the three-dimensional tissue models and were collected at different time points. A fibroblast-like change was observed when carcinoma cells infiltrating to the stromal lymphatic vessel.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

癌の悪性形質を制御する時計遺伝子（DEC1、DEC2）の機能を解明することにより、DEC1とDEC2を標的とする新たながん治療法（時計遺伝子DEC阻害剤薬）の開発と臨床応用研究への発展の可能性が期待できる。