| Project/Area Number |
25840011
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
Tanaka Yuji 高崎健康福祉大学, 薬学部, 助教 (90453422)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | リボソーム / rRNA転写 / ＫＤＭ２Ａ / ヒストン脱メチル化 / グルコース飢餓 / ＡＭＰＫ / ＴＮＢＣ / リボソームRNA / 転写 / KDM2A / 飢餓 / AMPK / TNBC / rRNA転写調節 / 乳がん / エピジェネティクス / JmjC / シグナル伝達 |
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| Outline of Final Research Achievements |
Previously, we found that serum and glucose starvation induces KDM2A activity to demethylate histone H3K36me2 on rDNA promoter and repress rRNA transcription. However, the molecular mechanism to control KDM2A is unclear.
In this study, we found the glucose starvation alone or 2-deoxyglucose (2DG), the inhibitor of glycolysis, could induce those KDM2A activities. Especially, low concentration of 2DG, that is mild starvation condition, induced those completely depended on KDM2A. The mild starvation could activate AMPK. The activity was required to induce the KDM2A activities. These KDM2A-dependent regulations existed in MCF-7 and MDA-MB-231 (TNBC) cells. In both cell-lines, mild starvation reduced cell proliferations dependent on KDM2A. In human breast cancer tissue, KDM2A were expressed in breast cancer cells independent on malignancy. These results suggested that mild starvation induced KDM2A-dependent demethylation and rRNA repression mediated by AMPK to control cell proliferation.
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