Involvement of the pioneer factor FoxA1 in breast cancer progression.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba University
• Principal Investigator: Noritaka Yamaguchi 千葉大学, 大学院薬学研究院, 准教授 (80399469)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: シグナル伝達

Outline of Final Research Achievements

FoxA1 is a pioneer factor that regulates chromatin remodeling and gene expression. FoxA1 is known to be involved in breast cancer progression through expression of genes controlling cell survival and growth. However, FoxA1 expression is reduced or lost in malignant types of breast cancer cells, and the relationship between the presence of FoxA1 expression and the malignancy of breast cancer cells has not been clarified. In this study, we found that loss of FoxA1 expression causes acquisition of chemo-resistance in breast cancer cells. This finding suggests that FoxA1 has both promotive and suppressive roles in breast cancer progression. Specific inhibition of its promotive roles in breast cancer progression is required for the treatment of breast cancer patients.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、クロマチン制御因子FoxA1が乳癌細胞の悪性化の促進と抑制の二面的な役割を持つことが明らかとなった。これまでの解析によってFoxA1が乳癌細胞の生存や増殖に寄与することが判明していたため、FoxA1の機能抑制が乳癌の治療に役立つと考えられてきたが、本研究によってFoxA1の機能抑制が薬剤抵抗性を誘導し乳癌の治療をより困難にする可能性が示された。今後、乳癌悪性化におけるFoxA1の促進的機能と抑制的機能について分子レベルの詳細な解析を進め、促進的機能のみを阻害する治療法開発を行う必要がある。