2020 Fiscal Year Final Research Report
Role of histone demethylase in breast cancer progression and finding new therapeutic approaches for breast cancer
| Project/Area Number |
18K06941
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | エピジェネティクス / 乳がん |
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| Outline of Final Research Achievements |
UTX is a histone demethylase that targets di- and tri-methylated histone H3 lysine 27 (H3K27me2/3) and KDM4B is a histone H3K9me2/3 demethylase. To study the effect of histone demethylase UTX and KDM4B loss on breast cancer in vivo, we have generated the mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) model of breast cancer lacking Utx or Kdm4b. We found that Utx deficiency accelerates tumor development and lung metastasis. Furthermore, breast tumor organoids isolated from Utx-deficient MMTV-PyMT mice showed highly invasive phenotype in 3D culture. These results suggested that deletion or decreased expression of UTX may promote human breast cancer progression, implicating clinical relevance of UTX in breast cancer treatment and/or diagnosis. On the other hand, loss of KDM4B suppressed the growth of mouse mammary tumor and prolonged the survival of MMTV-PyMT breast cancer mice. The inhibitor of KDM4B may have the therapeutic effect on breast cancer.
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| Free Research Field |
医歯薬学
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| Academic Significance and Societal Importance of the Research Achievements |
トリプルネガティブタイプ乳がんや転移性乳がんに対しては効果的な治療法が無いのが現状である。本研究によって、ヒストン脱メチル化酵素であるUTXの欠損は浸潤性の高い乳がん細胞を発生することが明らかとなった。UTXの欠失や発現の低下は乳がんの悪性化を促進し、乳がんの治療または診断におけるUTXの臨床的関連性があることが示唆された。一方、KDM4Bの欠損によって乳がんの発生・増殖が抑えられることから、KDM4Bの阻害剤が乳がんに対する新たな治療法となることが期待された。
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