| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
We identified three proteins(ERK1/2, DUSP3, HMGB1) which up-regulated phosphorylation and expression in adult T-cell lymphoma (ATL) cell-line comparing with HTLV-I immortalized human T-cells (MT-2) by proteomics. A correlation between expression level of ATL acute type clinical samples by immunohistochemistry and proteomics data in cell-line was found only for the HMGB1. Recurrent somatic mutation of STAT3 and HMGB1 was found in 32% and 24% of ATL acute type clinical samles, respectively.We hypothesized that STAT3 mutations may induce histone modifications, such as H3K9me3 and H3K9Ac, and may expedite STAT3 binding to the HMGB1 promoter in MT2. The reduction of H3K9me and elevation of H3K9Ac histone modification in the STAT3 binding sites on the promoter of HMGB1 was observed only in the STAT3 mutant. Tumor formation was observed in nude mice injected in MT-2 expressing STAT3 mutant and HMGB1 mutant. Forthermore,administration of HMGB1 inhibitor DHMEQ prevents tumor fomation.
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