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Molecular mechanisms of tumorigeneis in multiple endocrine neoplasia type 1 (MEN)

Research Project

Project/Area Number 23591346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionGunma University

Principal Investigator

OZAWA ATSUSHI  群馬大学, 医学部附属病院, 助教 (10573496)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords内分泌学 / 内分泌腫瘍 / 遺伝性腫瘍症 / 遺伝性疾患 / 膵ラ氏島 / 多発性内分泌腫瘍症1型 / MEN1 / 癌抑制遺伝子 / 膵内分泌腫瘍 / 多発性内分泌腫瘍症
Research Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome characterized by the occurrence of tumors in multiple endocrine tissues including parathyroid, enteropancreatic neuroendocrine and anterior pituitary. Although the tissue selectivity of tumors in specific endocrine organs is the essence of MEN1, the mechanisms underlying the tissue-specific tumorigenesis remain unknown. It is known that JunD and MLL, both transcription factors, are main binding partners of menin encoded by MEN1 gene. Through the analysis of mouse models and cDNA microarray, we investigated that JunD and MLL are the key molecules in tumorigenesis of endocrine tissues in MEN1.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (45 results)

All 2014 2013 2012 2011

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (20 results) Book (7 results)

  • [Journal Article] THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation.2013

    • Author(s)
      Katano-Toki A, Satoh T, Tomaru T, Yoshino S, Ishizuka T, Ishii S, Ozawa A, Shibusawa N, Tsuchiya T, Saito T, Shimizu H, Hashimoto K, Okada S, Yamada M, Mori M
    • Journal Title

      Molecular Endocrinology

      Volume: 27 Issue: 5 Pages: 769-780

    • DOI

      10.1210/me.2012-1332

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Humna stearoyl-CoA desaturase 1 (SCD-1) gene expression is negatively regulated by thyroid hormone without direct binding of thyroid hormone receptor to the gene promoter.2013

    • Author(s)
      Hashimoto K
    • Journal Title

      Endocrinology

      Volume: 154 Issue: 1 Pages: 537-549

    • DOI

      10.1210/en.2012-1559

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas2012

    • Author(s)
      Yamada M, Nakajima Y, Ozawa A, Mori M
    • Journal Title

      Endocr J

      Volume: 59 Pages: 735-741

    • NAID

      10031064823

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22863749

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] NR4A1 (Nur77) mediates thyrotropin-releasing hormone-induced stimulation of transcription of the thyrotropin β gene: analysis of TRH knockout mice.2012

    • Author(s)
      Nakajima Y
    • Journal Title

      PLos One

      Volume: 7 Issue: 7 Pages: e40437-e40437

    • DOI

      10.1371/journal.pone.0040437

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas.2012

    • Author(s)
      Taguchi R
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 97 Issue: 4 Pages: 1311-1319

    • DOI

      10.1210/jc.2011-2885

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple Endocrine Neoplasia Type 1in Japan : Establishment and Analysis of a Multicenter Database2012

    • Author(s)
      Sakurai, Akihiro ; Suzuki, Shinichi ; Kosugi, Shinji ; Okamoto, Takahiro ; Uchino, Shinya ; Miya, Akihiro ; Imai, Tsuneo ; Kaji, Hiroshi ; Komoto, Izumi ; Miura, Daishu ; Yamada, Masanobu ; Uruno, Takashi ; Horiuchi, Kiyomi
    • Journal Title

      European Review for Medical and Pharmacological Sciences

      Volume: 76(4) Issue: 4 Pages: 533-539

    • DOI

      10.1111/j.1365-2265.2011.04227.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked.2012

    • Author(s)
      Yamazaki M, Suzuki S, Kosugi S, Uchino S, Miura D, Yamada M, Miyauchi A, Imamura M, Sakurai A; MEN Consortium of Japan et al
    • Journal Title

      Endocr J

      Volume: 59 Pages: 797-807

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas.2012

    • Author(s)
      Yamada M, Nakajima Y, Taguchi R, Okamura T, Ishii S, Tomaru T, Ozawa A, Shibusawa N, Yoshino S, Toki A, Ishida E, Hashimoto K, Satoh T, Mori M.
    • Journal Title

      Endocr J

      Volume: 59 Pages: 735-741

    • NAID

      10031064823

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The tumor suppressor protein menin inhibits AKT activation by regulating its cellular localization2011

    • Author(s)
      Wang Y, Ozawa A, Marx SJ
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 2 Pages: 371-382

    • DOI

      10.1158/0008-5472.can-10-3221

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Haploinsufficient and Predominant Expression of Multiple Endocrine Neoplasia Type 1 (MEN1)-Related Genes, MLL, p27^<Kip1>and p18^<Ink4C>in Endocrine Organs2011

    • Author(s)
      Taguchi R, Yamada M, Horiguchi K, Ozawa A, Shibusawa N, Hashimoto K, Satoh T, Mori M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 415 Issue: 2 Pages: 378-383

    • DOI

      10.1016/j.bbrc.2011.10.077

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion2011

    • Author(s)
      Nakajima Y, Yamada M, Taguchi R, Satoh T, Hashimoto K, Ozawa A, Shibusawa N, Okada S, Monden T, Mori M
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 96 Issue: 8 Pages: 2512-2518

    • DOI

      10.1210/jc.2010-2743

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor2011

    • Author(s)
      Ishida E, Ozawa A, Mori M
    • Journal Title

      Endocr J

      Volume: 58 Pages: 287-96

    • NAID

      130004443685

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21441703

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver X receptor-α/βexpression ratio is increased in ACTH-secreting pituitary adenomas2011

    • Author(s)
      Hashimoto K, Matsumoto S, Ishida E, Miura A, Horiguchi K, Ozawa A, Shibusawa N, Satoh T, Yamada M, Yamada S, Mori M
    • Journal Title

      Neurosci Lett

      Volume: 494 Issue: 1 Pages: 34-37

    • DOI

      10.1016/j.neulet.2011.02.048

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs.2011

    • Author(s)
      Taguchi R, Yamada M, Horiguchi K, Tomaru T, Ozawa A, Shibusawa N, Hashimoto K, Okada S, Satoh T, Mori M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 415 Pages: 378-383

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion.2011

    • Author(s)
      Nakajima Y, Yamada M, Taguchi R, Satoh T, Hashimoto K, Ozawa A, Shibusawa N, Okada S, Monden T, Mori M.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 96 Pages: 2512-2518

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor.2011

    • Author(s)
      Ishida E, Yamada M, Horiguchi K, Taguchi R, Ozawa A, Shibusawa N, Hashimoto K, Satoh T, Yoshida S, Tanaka Y, Yokota M, Tosaka M, Hirato J, Yamada S, Yoshimoto Y, Mori M.
    • Journal Title

      Endocr J.

      Volume: 58 Pages: 287-296

    • NAID

      130004443685

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver X receptor-α/β expression ratio is increased in ACTH-secreting pituitary adenomas.2011

    • Author(s)
      Hashimoto K, Matsumoto S, Ishida E, Miura A, Horiguchi K, Ozawa A, Shibusawa N, Satoh T, Yamada M, Yamada S, Mori M.
    • Journal Title

      Neurosci Lett.

      Volume: 494 Pages: 34-37

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 多発性内分泌腫瘍の病態生理と臨床像2011

    • Author(s)
      小澤厚志, 山田正信
    • Journal Title

      日本臨床

      Volume: 69巻増刊2 Pages: 681-685

    • Related Report
      2011 Research-status Report
  • [Presentation] Distinct expression of splicing variants of the human MEN1 (multiple endocrine neoplasia type 1) gene in various pituitary adenomas2014

    • Author(s)
      Atsushi Ozawa, Takuya Watanabe 他
    • Organizer
      11^<th> Annual ENETS (European neuroendocrine tumor society) conference
    • Place of Presentation
      バルセロナ、スペイン
    • Related Report
      2013 Final Research Report
  • [Presentation] ラ氏島の腫瘍化機構におけるmenin-JunD共役結合の役割:モデルマウスの樹立とマイクロアレイ解析2014

    • Author(s)
      小澤厚志、渡邉琢也、佐藤哲郎、中島康代、登丸琢也、石井角保、渋沢信行、岡田秀一、森 昌朋、山田正信
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト下垂体腺腫における多発性内分泌腫瘍症1型(MEN1)遺伝子Splicing variantの発現解析2014

    • Author(s)
      小澤厚志、渡邉琢也、登坂雅彦、好本裕平、土岐明子、中島康代、登丸琢也、石井角保、渋沢信行、橋本貢士、岡田秀一、佐藤哲郎、山田正三、森昌朋、山田正信
    • Organizer
      第87回日本内分泌学会学術総会抄録集
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] Distinct expression of splicing variants of the human MEN1 (multiple endocrine neoplasia type 1) gene in various pituitary adenomas.2014

    • Author(s)
      Atsushi Ozawa, Takuya Watanabe, Masahiko Tosaka, Yuhei Yoshimoto, Kazuhiko Horiguchi, Yasuyo Nakajima, Takuya Tomaru, Sumiyasu Ishii, Nobuyuki Shibusawa, Shuichi Okada, Tetsurou Satoh, Masanobu Yamada.
    • Organizer
      11th Annual ENETS (European neuroendocrine tumor society) conference.
    • Place of Presentation
      バルセロナ、スペイン
    • Related Report
      2013 Annual Research Report
  • [Presentation] 変異JunDによる膵神経内分泌腫瘍発症機構の解明:膵β細胞特異的変異JunDトランスジェニックマウスの作製と解析2013

    • Author(s)
      小澤厚志、渡邉琢也 他
    • Organizer
      第40回日本神経内分泌学会学術集会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Final Research Report
  • [Presentation] MEN1遺伝子Exon1 splicing variantの腫瘍組織における発現解析2013

    • Author(s)
      小澤厚志、山田正信 他
    • Organizer
      第19回日本家族性腫瘍学会学術集会
    • Place of Presentation
      別府
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵β細胞腫瘍発症への変異JunDの関与:β細胞特異的変異JunDトランスジェニックマウスの解析2013

    • Author(s)
      小澤厚志、山田正信 他
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] 下垂体におけるMEN1遺伝子Exon1 splicing variantの発現解析2013

    • Author(s)
      小澤厚志、山田正信 他
    • Organizer
      第23回日本間脳下垂体腫瘍学会学術総会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Final Research Report
  • [Presentation] 変異JunDによる膵神経内分泌腫瘍発症機構の解明:膵β細胞特異的変異JunDトランスジェニックマウスの作製と解析2013

    • Author(s)
      小澤厚志、渡邉琢也、岡村孝志、田口 亮、吉野 聡、中島康代、登丸琢也、石井角保、渋沢信行、橋本貢士、岡田秀一、佐藤哲郎、森 昌朋、山田正信
    • Organizer
      第40回日本神経内分泌学会学術集会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] MEN1遺伝子Exon1 splicing variantの腫瘍組織における発現解析2013

    • Author(s)
      小澤厚志、田口 亮、登丸琢也、石井角保、渋沢信行、佐藤哲郎、森 昌朋、山田正信
    • Organizer
      第19回日本家族性腫瘍学会学術集会
    • Place of Presentation
      別府
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵島腫瘍発症機構における転写因子JunDの役割:膵β細胞特異的変異JunDトランスジェニックマウスの作製と解析2013

    • Author(s)
      小澤厚志、山田正信、田口 亮、渋沢信行、岡村孝志、土岐明子、石田恵美、吉野聡、中島康代、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森 昌朋
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵β細胞腫瘍発症への変異JunDの関与:β細胞特異的変異JunDトランスジェニックマウスの解析2013

    • Author(s)
      小澤厚志、山田正信、田口 亮、Jennifer Garay Guerrero、渋沢信行、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森 昌朋
    • Organizer
      第87回日本内分泌学会学術総会抄録集
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵島腫瘍発症機構における転写因子JunDの役割2013

    • Author(s)
      小澤厚志、山田正信、田口亮、渋沢信行、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森昌朋
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵β細胞腫瘍発症への変異JunDの関与2013

    • Author(s)
      小澤厚志、山田正信、田口亮、Jennifer Garay Guerrero, 渋沢信行、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森昌朋
    • Organizer
      第86回日本内分泌学会学術集会
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
  • [Presentation] 下垂体におけるMEN1遺伝子Exon1 splicing variantの発現解析2013

    • Author(s)
      小澤厚志、山田正信、田口亮、渋沢信行、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森昌朋
    • Organizer
      第23回日本間脳下垂体腫瘍学会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Research-status Report
  • [Presentation] 多発性内分泌腫瘍症1型(MEN1)モデルマウスの解析:臓器特異的腫瘍発症機構の解明2012

    • Author(s)
      小澤厚志、山田正信 他
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] MEN1遺伝子Exon1 splicing variantの組織間における発現解析2012

    • Author(s)
      小澤厚志、山田正信、田口亮、渋沢信行、登丸琢也、石井角保、橋本貢士、佐藤哲郎、森昌朋
    • Organizer
      第39回日本神経内分泌学会学術集会
    • Place of Presentation
      北九州
    • Related Report
      2012 Research-status Report
  • [Presentation] 多発性内分泌腫瘍症1型(MEN1)モデルマウスの解析 臓器特異的腫瘍発症機構の解明2012

    • Author(s)
      小澤厚志、山田正信、田口亮、渋沢信行、登丸琢也、橋本貢士、佐藤哲郎、森昌朋
    • Organizer
      第85回日本内分泌学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 多発性内分泌腫瘍症1型の組織特異的腫瘍発生分子メカニズムの解明ーモデルマウスの解析2011

    • Author(s)
      小澤厚志、Jennifer Garay Guerrero、田口 亮、山田正信、森 昌朋
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      神戸国際展示場(神戸)
    • Related Report
      2011 Research-status Report
  • [Presentation] 変異JunDによる膵内分泌腫瘍発症機構:マウスモデルの解析2011

    • Author(s)
      小澤厚志、山田正信、田口 亮、登丸琢也、渋沢信行、橋本貢士、佐藤哲郎、森 昌朋
    • Organizer
      第38回日本神経内分泌学会学術集会
    • Place of Presentation
      都道府県会館(東京)
    • Related Report
      2011 Research-status Report
  • [Book] 臨床検査ガイド2013〜20142013

    • Author(s)
      小澤厚志他
    • Publisher
      文光堂
    • Related Report
      2013 Final Research Report
  • [Book] ホルモンと臨床【内分泌腫瘍発症機構に迫る】2013

    • Author(s)
      小澤厚志、山田正信
    • Total Pages
      89
    • Publisher
      医学の世界社
    • Related Report
      2013 Annual Research Report
  • [Book] ホルモンと臨床【膵内分泌腫瘍】2013

    • Author(s)
      小澤厚志、山田正信
    • Total Pages
      72
    • Publisher
      医学の世界社
    • Related Report
      2013 Annual Research Report
  • [Book] 臨床検査ガイド2013~20142013

    • Author(s)
      小澤厚志、森 昌朋
    • Total Pages
      1107
    • Publisher
      文光堂
    • Related Report
      2013 Annual Research Report
  • [Book] ホルモンと臨床「内分泌腫瘍発症機構に迫る」2012

    • Author(s)
      小澤厚志他
    • Publisher
      医学の世界社
    • Related Report
      2013 Final Research Report
  • [Book] ホルモンと臨床「膵内分泌腫瘍」2012

    • Author(s)
      水出雅文、小澤厚志他
    • Publisher
      医学の世界社
    • Related Report
      2013 Final Research Report
  • [Book] ホルモンと臨床「膵内分泌腫瘍」2012

    • Author(s)
      小澤厚志他
    • Publisher
      医学の世界社
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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