| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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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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