| Project/Area Number |
24590373
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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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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
TANAKA Yujiro 東京医科歯科大学, 難治疾患研究所, 准教授 (00311613)
KAWAUCHI Junya 東京医科歯科大学, 難治疾患研究所, 助教 (20544498)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ストレス応答 / 遺伝子改変マウス / ＡＴＦ３ / ｐ５３ / 抗がん剤 / 細胞死受容体 / ＤＲ５ / ストレス応答遺伝子 / ATF3 / p53 / Wnt / モデルマウス / 抗がん治療 / がん抑制 / 発がん / 動物モデル / TRAIL受容体 |
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| Outline of Final Research Achievements |
Stress response of cancer cells plays pivotal role in determining output of various anti-cancer therapy. In this project, we generated double KO mice of p53 and stress response gene ATF3 and demonstrated that DKO mice developed earlier and more severe cancers and resulted in lower survival than p53 KO. Mass spectrometry of ATF3 complex identified different sets of protein components between ATF3 tumor suppressor complex and oncogene complex. However, TP53BP1 was present in both complexes. It was also found that several anti-cancer agents activated the expression of death receptor 5 (DR5) on the surface of cancer cells, sensitizing them to TRAIL or DR5 agonist. This activity is mediated by p53-ATF3 or ROS-ER stress response, providing molecular basis for useful combined therapy of conventional anti-cancer agents and DR5 agonists.
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