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2018 Fiscal Year Final Research Report

Elucidation of novel androgen response gene activated by AR splicing variant of prostate cancer

Research Project

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Project/Area Number 16K11011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionNagasaki University

Principal Investigator

SHIDA Yohei  長崎大学, 病院(医学系), 助教 (40641337)

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)
Research Collaborator NAKAGAWA Takeya  
Project Period (FY) 2016-04-01 – 2019-03-31
KeywordsAR-V7 / Full-length AR / in vitro 転写 / DHT
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.

Free Research Field

泌尿器科学

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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Published: 2020-03-30  

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