Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor

• Kanno Yuichiro

  Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University

• Zhao Shuai

  Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University

• Yamashita Naoya

  Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University

• Yanai Kazuyuki

  Department of Biomolecular Science, Faculty of Science, Toho University

• Nemoto Kiyomitsu

  Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University

• Inouye Yoshio

  Department of Molecular Toxicology, Faculty of Pharmaceutical Sciences, Toho University

抄録

It has been noticed that crosstalk between androgen receptor (AR) and mammalian target of rapamycin (mTOR) signaling pathways plays a crucial role in the proliferation of prostate cancer cells. To clarify this mechanism, we focused on DEPTOR, a naturally occurring inhibitor of mTOR. The treatment of a human AR-positive prostate cancer cell line, LNCaP, with the AR-agonist dihydrotestosterone (DHT) repressed DEPTOR mRNA expression in a time-dependent manner. This repression was abrogated by treatment with the AR-antagonist bicalutamide. Knockdown of DEPTOR mRNA by siRNA resulted in the increased phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (S6K), a substrate of mTORC1, accompanied by the elevated expression of cyclin D1, a positive regulator of cell proliferation. Furthermore, the ChIP assay demonstrated that AR could bind to AR-responsible element-like region within the 4th intron of the DEPTOR gene. The amount of acetylated histone H3 (Lys9, Lys14) was reduced by the DHT treatment in this region. Taken together, these results propose that AR-dependent prostate cancer cell proliferation requires decreased DEPTOR transcription directly controlled by AR.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 40 (6), 753-758, 2015

  一般社団法人　日本毒性学会

キーワード

• Androgen receptor
• mTOR
• DEPTOR
• Prostate cancer

詳細情報

• CRID: 1390282679880086912
• NII論文ID: 130005108863
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.40.753
• ISSN: 18803989
• ISSN: 03881350
• NDL書誌ID: 026971343
• PubMed: 26558456
• Web Site: http://id.ndl.go.jp/bib/026971343
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026971343
• Web Site: https://www.jstage.jst.go.jp/article/jts/40/6/40_753/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016248645
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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