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Identification and analysis of new androgen responsive regulatory genes for development and cancer.

Research Project

Project/Area Number 15H04300
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionWakayama Medical University

Principal Investigator

Yamada Gen  和歌山県立医科大学, 先端医学研究所, 教授 (80174712)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsアンドロゲン / 男性ホルモン / bZipファミリー / 癌関連繊維芽細胞 / MafB / 生殖器間葉細胞 / 外生殖器 / 前立腺 / 癌繊維芽細胞 / 前立腺癌 / エンハンサー / アンドロゲンレセプター / 発生制御 / 発現制御 / 雄性化 / ホルモン
Outline of Final Research Achievements

The current study suggests that the Mafb 3' untranslated region (UTR) is an essential region for its regulation by androgen. We identified 2 functional androgen response elements (AREs) in Mafb 3UTR.
Androgen receptor is bound to such AREs in 3UTR during urethral masculinization. By using such identified UTR-enhancer, we revealed new candidate upstream gene for MafB regulation. Our ongoing study suggests such new transcription factor-AR interaction is essential for regulating MafB enhancer. CAF cells have been also suggested as playing essential role for prostate cancer. The current study gives insight for the regulation of bZip family gene function not only in embryonic mesenchyme cells but also for cancer associated fibroblast (CAF) cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (35 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (5 results) Journal Article (16 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 16 results,  Open Access: 5 results,  Acknowledgement Compliant: 6 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Remarks (6 results)

  • [Int'l Joint Research] University of Minnesota、ミネソタ州/NHLBI/NIH、メリーランド州/Cleveland Clinic、オハイオ州(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Bonn(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Bonn Clinics(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Department of Developmental Biology/Washington University School of Medicine(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Department of Surgery/The university of Hong Kong(中国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Frontiers in the regulation of masculinization; androgen signaling in the developing external genitalia.2018

    • Author(s)
      Shoko Matsushita, Kentaro Suzuki, Aki Murashima, Daiki Kajioka, Alvin Acebedo, Shinichi Miyagawa, Ryuma Haraguchi, Yukiko Ogino, and Yamada G.
    • Journal Title

      Nature Reviews Urology

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR.2018

    • Author(s)
      Yukiko Ogino, Saki Tohyama, Satomi Kohno, Kenji Toyota, Gen Yamada, Ryohei Yatsu, Tohru Kobayashi, Norihisa Tatarazako, Tomomi Sato, Hajime Matsubara, Anke Lange, Charles R. Tyler, Yoshinao Katsu, Taisen Iguchi, Shinichi Miyagawa.
    • Journal Title

      Journal of Steroid Biochemistry and Molecular Biology

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 5α-Dihydrotestosterone negatively regulates cell proliferation of the periurethral ventral mesenchyme during urethral tube formation in the murine male genital tubercle2017

    • Author(s)
      Hiroko Suzuki, Shoko Matsushita, Kentaro Suzuki, Gen Yamada
    • Journal Title

      Andrology

      Volume: 5 Issue: 1 Pages: 146-152

    • DOI

      10.1111/andr.12241

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Epispadias and the associated embryopathies; genetic and developmental basis.2017

    • Author(s)
      Kentaro Suzuki, Daisuke Matsumaru, Shoko Matsushita, Aki Murashima, Michael Ludwig, Heiko Reuter, Gen Yamada
    • Journal Title

      Clinical Genetics

      Volume: 91 Issue: 2 Pages: 247-253

    • DOI

      10.1111/cge.12871

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Establishment of estrogen receptor 1 (ESR1)-knockout medaka; ESR1 is dispensable for sexual development and reproduction in medaka, Oryzias latipes.2017

    • Author(s)
      Tohyama S, Ogino Y, Lange A, Myosho T, Kobayashi T, Hirano Y, Yamada G, Sato T, Tatarazako N, Tyler CR, Iguchi T, Miyagawa S.
    • Journal Title

      Dev Growth Diff

      Volume: 59 Issue: 6 Pages: 552-561

    • DOI

      10.1111/dgd.12386

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Developmental Contribution of Wnt-signal-responsive Cells to Mouse Reproductive Tract Formation2017

    • Author(s)
      Haraguchi Ryuma, Kitazawa Riko, Murashima Aki, Yamada Gen, Kitazawa Sohei
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 50 Issue: 4 Pages: 127-133

    • DOI

      10.1267/ahc.17017

    • NAID

      130006003857

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Androgen Regulates Dimorphic F-Actin Assemblies in the Genital Organogenesis2017

    • Author(s)
      Liu Liqing、Suzuki Kentaro、Chun Eunice、Murashima Aki、Sato Yuki、Nakagata Naomi、Fujimori Toshihiko、Yonemura Shigenobu、He Wanzhong、Yamada Gen
    • Journal Title

      Sexual Development

      Volume: 11 Issue: 4 Pages: 190-202

    • DOI

      10.1159/000477452

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression patterns of Fgf8 and Shh in the developing externalgenitalia of Suncus murinus.2017

    • Author(s)
      Miyado M, Miyado K, Nakamura A, Fukami M, Yamada G, Oda SI.
    • Journal Title

      Reproduction

      Volume: 153(2) Pages: 187-195

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression patterns of Fgf8 and Shh in the developing external genitalia of Suncus murinus.2017

    • Author(s)
      Miyado M, Miyado K, Nakamura A, Fukami M, Yamada G, Oda SI.
    • Journal Title

      Reproduction.

      Volume: 153(2) Pages: 187-195

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.2017

    • Author(s)
      Zhang R, Knapp M, Suzuki K...Yamada G, Odermatt B, Reutter H.
    • Journal Title

      Sci Rep.

      Volume: 8;7 Issue: 1 Pages: 42170-42170

    • DOI

      10.1038/srep42170

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Genetics of Bladder-Exstrophy-Epispadias Complex (BEEC): Systematic Elucidation of Mendelian and Multifactorial Phenotypes.2016

    • Author(s)
      Reutter H, Keppler-Noreuil K, E Keegan C, Thiele H, Yamada G, Ludwig M.
    • Journal Title

      Curr Genomics.

      Volume: 17(1) Issue: 1 Pages: 4-13

    • DOI

      10.2174/1389202916666151014221806

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Neofunctionalization of androgen receptor by gain-of-function mutations in teleost fish lineage2016

    • Author(s)
      Ogino Y, Kuraku S, Ishibashi H, Miyakawa H, Sumiya E, Miyagawa S, Matsubara H, Yamada G, Baker ME, Iguchi T
    • Journal Title

      Mol Biol Evol

      Volume: 33 Issue: 1 Pages: 228-244

    • DOI

      10.1093/molbev/msv218

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Androgen regulates Mafb expression through its 3’UTR during mouse urethral masculinization2016

    • Author(s)
      Matsushita S, Suzuki K, OginoY, Hino S, Sato T, Suyama M, Matsumoto T, Omori A, Inoue S, Yamada G
    • Journal Title

      Endocrinology

      Volume: 157 Issue: 2 Pages: 844-857

    • DOI

      10.1210/en.2015-1586

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Region-specific regulation of cell proliferation by Fgf receptor signaling during the Wolffian duct development2015

    • Author(s)
      Mika Okazawa, Aki Murashima, Masayo Harada, Naomi Nakagata, Masafumi Noguchi, Mitsuru Morimoto, Tadashi Kimura, David M. Ornitz, Gen Yamada
    • Journal Title

      Developmental Biology

      Volume: 1;400(1) Issue: 1 Pages: 139-147

    • DOI

      10.1016/j.ydbio.2015.01.023

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Systematic stereoscopic analyses for cloacal development: The origin of anorectal malformations.2015

    • Author(s)
      Matsumaru D, Murashima A, Fukushima J, Senda S, Matsushita S, Nakagata N, Miyajima M, Yamada G.
    • Journal Title

      Sci Rep.

      Volume: 10;5 Issue: 1 Pages: 13943-13943

    • DOI

      10.1038/srep13943

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systematic analyses of murine masculinization processes based on genital sex differentiation parameters2015

    • Author(s)
      Suzuki H, Suzuki K, Yamada G
    • Journal Title

      Dev Growth Differ.

      Volume: 57(9) Issue: 9 Pages: 639-647

    • DOI

      10.1111/dgd.12247

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Frontier of cell migration analysis; androgen development mouse genitalia formation based on the mutant model analysis.2017

    • Author(s)
      山田 源
    • Organizer
      The 25th International syposia on Morphological Sciences (ISMS 2017)、第4軍医大学、中国
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanisms of external genitalia formation; an emerging model for hormone-induced organogenesis.2017

    • Author(s)
      山田 源
    • Organizer
      Reproduction down under 2017、Mantra on Salt Beach、オーストラリア
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] “Androgen and local signal interaction for mouse sexual differentiation”2016

    • Author(s)
      山田 源
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜 (横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] “Molecular mechanisms of sexual differentiation; Genetic cascade responsible for sexual reproductive organ formation and diseases, cancer”2016

    • Author(s)
      Gen Yamada
    • Organizer
      Philippine society for cell biology (PSCB) meeting (7th Annual and 1st International convention and scientific meeting)
    • Place of Presentation
      Institute of Biology, University of the Philippines, Diliman (フィリピン)
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「マウスミュータント系を用いた生殖器形成の解明の最前線:性差は如何に制御されるか」2016

    • Author(s)
      山田 源
    • Organizer
      第53回 北陸実験動物研究会
    • Place of Presentation
      金沢大学 (金沢市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanisms of sexual differentiation; recent mouse models2015

    • Author(s)
      Gen Yamada
    • Organizer
      Lerner Research Institute Seminar
    • Place of Presentation
      Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland Ohio, USA
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 外生殖器形成機構の最新研究2015

    • Author(s)
      山田 源
    • Organizer
      第55回日本先天異常学会学術集会及び第38回日本小児遺伝学会学術集会
    • Place of Presentation
      パシフィコ横浜会議センター
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Development of the external genitalia2015

    • Author(s)
      Gen Yamada
    • Organizer
      I-DSD symposium, 5th International DSD symposium
    • Place of Presentation
      New Zebra, Ghent, Belsium
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] Department of Developmental Genetics, WMU

    • URL

      http://www.wakayama-med.ac.jp/english/undergraduate/medicine/160904/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] Research Gate, Gen Yamada

    • URL

      http://www.researchgate.net/profile/Gen_Yamada

    • Related Report
      2017 Annual Research Report
  • [Remarks] WMU, Department Of Developmental Genetics

    • URL

      http://www.wakayama-med.ac.jp/english/undergraduate/medicine/160904/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] ResearchGate, Gen Yamada

    • URL

      https://www.researchgate.net/profile/Gen_Yamada/

    • Related Report
      2016 Annual Research Report
  • [Remarks] Wakayama Medical University

    • URL

      http://www.wakayama-med.ac.jp/english/undergraduate/medicine/genetics.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 和歌山県立医科大学 遺伝子制御学研究部

    • URL

      http://www.wakayama-med.ac.jp/dept/igakubu/160904/index.html

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-02-28  

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