Elucidation of novel androgen response gene activated by AR splicing variant of prostate cancer
| Project/Area Number |
16K11011
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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 |
Urology
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| Research Institution | Nagasaki University |
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Principal Investigator |
SHIDA Yohei 長崎大学, 病院(医学系), 助教 (40641337)
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| Co-Investigator(Kenkyū-buntansha) |
計屋 知彰 長崎大学, 医歯薬学総合研究科(医学系), 助教 (00716574)
宮田 康好 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (60380888)
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| Research Collaborator |
NAKAGAWA Takeya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | AR-V7 / Full-length AR / in vitro 転写 / DHT / アンドロゲン受容体（AR） / full-length AR / adenovirus E4 プロモーター / エンザルタミド / ビカルタミド / PC-3 / AR-V567es / PSA / 腫瘍学 |
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| Outline of Final Research Achievements |
We prepared plasmid DNA of several novel androgen responsive genes for chromatin templates and determined the difference in transcriptional activation between full-length AR and AR-V7 using an original in vitro transcriptional system. However, there were no difference. Next, we prepared a plasmid construct with five copies of the positive androgen-response element upstream of the adenovirus E4 core promoter (pARE) for a chromatin template. With this system, we observed transcriptional activation, both by purified full-length AR and by AR-V7. As expected, dihydrotestosterone (DHT) significantly enhanced full-length AR transcription. Although AR-V7 lacks the previously identified hormone-binding domain, it also stimulated transcription following the addition of DHT.
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| Academic Significance and Societal Importance of the Research Achievements |
完全長AR、AR-V7による遺伝子転写を再現するin vitro転写システムを独自に作製して実験を行った結果、既知のリガンド結合領域を欠くにもかかわらず、AR-V7による転写も完全長AR同様にDHTによって強く活性化されることを見出した。今回の結果は、これまで諸家から報告されている臨床研究結果や細胞を用いた実験結果とは異なっていた。今後さらに解析を進めることで、AR-V7によるアンドロゲン応答性遺伝子転写の未知のメカニズムの解明や、前立腺癌の薬剤耐性メカニズムの解析に寄与できるのではないかと考える。
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Report
(4 results)
Research Products
(3 results)
