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2013 Fiscal Year Final Research Report

Flexibility of intracellular estrogen signaling pathway and mechanism of aromatase inhibitor-resistance

Research Project

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Project/Area Number 23591344
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAYASHI Shinichi  東北大学, 医学(系)研究科(研究院), 教授 (60144862)

Project Period (FY) 2011 – 2013
Keywordsエストロゲン / ホルモン療法耐性 / アロマターゼ阻害薬 / MCF-7細胞 / 乳癌 / シグナル伝達 / GFP / アンドロゲン
Research Abstract

To elucidate the aromatase inhibitor (AI)-resistant mechanism, we established 6 kinds of resistant cell lines having different resistant mechanisms from ERE-GFP introduced MCF-7 cells which we established previously. These resistant cells were established by long-term estrogen depletion and/or androgen supplemented under monitoring ERE-GFP activity. The characterization of these cell lines revealed novel hormonal therapy-resistant mechanisms such as ligand-independent ER activation by phosphorylation from PI3K-Akt pathway, ER activation by estrogen-like androgen metabolite (3bHSD), or androgen receptor-dependent growth mechanism.

  • Research Products

    (52 results)

All 2014 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 11 results) Presentation (37 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Detection of estrogen-independent growth-stimulating activity in breast cancer tissues : implication for tumor aggressiveness2014

    • Author(s)
      Yamaguchi Y, Seino Y, Takei H, Kurosumi M, and Hayashi S
    • Journal Title

      Cancer Microenvironment

      Volume: (in press)

  • [Journal Article] Variation in use of estrogen receptor a gene promoters in breast cancer compared by quantification of promoter-specific mRNA2014

    • Author(s)
      Higuchi T, Gohno T, Nagatomo T, Tokiniwa H, Niwa T, Horiguchi J, Oyama T, Takeyoshi I, Hayashi S
    • Journal Title

      Clin. Breast Cancer

      Volume: (in press)

  • [Journal Article] Possible role of the aromatase- independent steroid metabolism pathways in hormone responsive primary breast cancers2014

    • Author(s)
      Hanamura T, Niwa T, Gohno T, Kurosumi M, Takei H, Yamaguchi Y, Ito K, Hayashi S
    • Journal Title

      Breast Cancer Res. Treat

      Volume: 143(1) Pages: 69-80

    • DOI

      10.1007/s10549-013-2788-3

    • Peer Reviewed
  • [Journal Article] Estrogen response element-GFP (ERE-GFP) introduced MCF-7 cells demonstrated the coexistence of multiple estrogen- deprivation resistant mechanisms2014

    • Author(s)
      Fujiki N, Konno H, Kaneko Y, Gohno T, Hanamura T, Imami K, Ishihama Y, Nakanishi K, Niwa T, Seino Y, Yamaguchi Y, Hayashi S
    • Journal Title

      J. Steriod Biochem. Mol. Biol.

      Volume: 139 Pages: 61-72

    • DOI

      10.1016/j.jsbmb.2013.08.012

    • Peer Reviewed
  • [Journal Article] Androgen metabolite- dependent growth of hormone receptor- positive breast cancer as a possible aromatase inhibitor-resistance mechanism2013

    • Author(s)
      Hanamura T, Niwa T, Nishikawa S, Konno H, Gohno T, Tazawa C, Kobayashi Y, Kurosumi M, Takei H, Yamaguchi Y, Ito K, Hayashi S
    • Journal Title

      Breast Cancer Res. Treat

      Volume: 139(3) Pages: 731-740

    • DOI

      10.1007/s10549-013-2595-x

    • Peer Reviewed
  • [Journal Article] Intratumoral estrogen concentration and expression of estrogen-induced genes in male breast carcinoma : comparison with female breast carcinoma2013

    • Author(s)
      Takagi K, Moriya T, Kurosumi M, Oka K, Miki Y, Ebata A, Toshima T, Tsunekawa S, Takei H, Hirakawa H, Ishida T, Hayashi S, Kurebayashi J, Sasano H, Suzuki T
    • Journal Title

      Hormones and Cancer

      Volume: 4(1) Pages: 1-11

    • DOI

      10.1007/s12672-012-0126-6

    • Peer Reviewed
  • [Journal Article] Individual transcription activity of estrogen receptors in primary breast cancer and its clinical significance2012

    • Author(s)
      Gohno T, Seino Y, Hanamura T, Niwa T, Matsumoto M, Yaegashi N, Oba H, Kurosumi M, Takei H, Yamaguchi Y, Hayashi S
    • Journal Title

      Cancer Medicine

      Volume: 1(3) Pages: 328-337

    • DOI

      10.1002/cam4.41

    • Peer Reviewed
  • [Journal Article] ER-activating ability of breast cancer stromal fibroblasts is regulated independently of alteration of TP53 and PTEN tumor suppressor genes2012

    • Author(s)
      Suda T, Oba H, Takei H, Kurosumi M. Hayashi S, Yamaguchi Y
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 428 Pages: 259-263

    • DOI

      10.1016/j.bbrc.2012.10.035

    • Peer Reviewed
  • [Journal Article] Antitumor activity of chemo-endocrine therapy in premenopausal and postmenopausal models with human breast cancer xenografts2012

    • Author(s)
      Kataoka M, Yamaguchi Y, Moriya Y, Sawada N, Yasuno H, Kondoh K, Evans DB, Mori K, and Hayashi S
    • Journal Title

      Oncology Reports

      Volume: 27 Pages: 303-310

    • DOI

      10.3892/or.2011.1541

    • Peer Reviewed
  • [Journal Article] Estrogen receptor-αdirectly regulates sensitivity to paclitaxel in neoadjuvant chemotherapy for breast cancer2012

    • Author(s)
      Tokuda E, Seino Y, Arakawa A, Saito M, Kasumi F, Hayashi S, and Yamaguchi Y
    • Journal Title

      Breast Cancer Res. Treat.

      Volume: 133(2) Pages: 427-36

    • DOI

      10.1007/s10549-011-1758-x

    • Peer Reviewed
  • [Journal Article] Effects of S-equol and natural S-equol supplement (SE5-OH) on the growth of MCF-7 in vitro and as tumors implanted into ovariectomized athymic mice2011

    • Author(s)
      Onoda A, Ueno T, Uchiyama S, Hayashi S, Kato K, Wake N
    • Journal Title

      Food Chem Toxicol

      Volume: 49(9) Pages: 2279-2284

    • DOI

      10.1016/j.fct.2011.06.027

    • Peer Reviewed
  • [Journal Article] Identification of a GPER/GPR30 antagonistwithimproved estrogen receptor counterselectivity2011

    • Author(s)
      Dennis MK, Field AS, Burai R, Ramesh C, Petrie WK, Bologa CG, Oprea TI, Yamaguchi Y, Hayashi S, Sklar SLA, Hathaway HJ, Arterburn, JB, and Prossnitz ER
    • Journal Title

      J. Steroid Biochem. Mol. Biol.

      Volume: 127 Pages: 358-366

    • DOI

      10.1016/j.jsbmb.2011.07.002

    • Peer Reviewed
  • [Journal Article] Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene-3ß, 17ß-diol2011

    • Author(s)
      Honma N, Saji S, Hirose M, Horiguchi S, Kuroi K, Hayashi S, Ustumi T, Harada N
    • Journal Title

      Cancer Sci.

      Volume: 102 Pages: 1848-1854

    • DOI

      10.1111/j.1349-7006.2011.07.002

    • Peer Reviewed
  • [Presentation] アンドロゲン受容体依存性増殖を示すアロマターゼ阻害剤耐性モデル乳癌細胞2013

    • Author(s)
      藤井里圭、花村徹、丹羽俊文、笹野公伸、石田孝宣、大内憲明、林慎一
    • Organizer
      第14回ホルモンとがん研究会
    • Place of Presentation
      東京
    • Year and Date
      20130712-13
  • [Presentation] Estrone Sulfate依存性Aromatase Inhibitor耐性ヒト乳癌細胞株の増殖機構2013

    • Author(s)
      樋口徹、遠藤恵、花村徹、郷野辰幸、丹羽俊文、山口ゆり、堀口淳、竹吉泉、林慎一
    • Organizer
      第21回日本乳癌学会学術総会
    • Place of Presentation
      浜松
    • Year and Date
      20130627-29
  • [Presentation] 閉経後ホルモン感受性乳癌におけるAndrogen代謝によるAromatase非依存性ER活性化機構と新規治療の可能性2013

    • Author(s)
      花村徹、丹羽俊文、郷野辰幸、山口ゆり、黒住昌史、武井寛幸、伊藤研一、林慎一
    • Organizer
      第21回日本乳癌学会学術総会
    • Place of Presentation
      浜松
    • Year and Date
      20130627-29
  • [Presentation] アンドロゲン受容体(AR)依存性増殖を示すアロマターゼ阻害剤(AI)耐性モデル乳癌細胞株2013

    • Author(s)
      藤井里圭、花村徹、丹羽俊文、石田孝宣、大内憲明、林慎一
    • Organizer
      第21回日本乳癌学会学術総会
    • Place of Presentation
      浜松
    • Year and Date
      20130627-29
  • [Presentation] The androgen metabolite-dependent growth of hormone receptor positive breast cancer as a possible aromatase inhibitor-resistance mechanism2013

    • Author(s)
      Toru Hanamura, Toshifumi Niwa, Sayo Nishikawa, Hiromi Konno, Tatsuyuki Gohno, Chika Tazawa, Yasuhito Kobayashi, Masafumi Kurosumi, Hiroyuki Takei, Yuri Yamaguchi, Ken-ichi Ito, Shin-ichi Hayashi
    • Organizer
      American Association for Cancer Research ANNUAL MEETING 2013
    • Place of Presentation
      Washington
    • Year and Date
      20130406-10
  • [Presentation] ER陽性閉経後乳癌治療とClinical Question2013

    • Author(s)
      林慎一
    • Organizer
      Breast Cancer Scientific Exchange Meeting in Sendai
    • Place of Presentation
      仙台
    • Year and Date
      2013-07-02
  • [Presentation] Luminal型乳癌のトランスレーショナルリサーチについて2013

    • Author(s)
      林慎一
    • Organizer
      第21回日本乳癌学会学術総会シンポジウム
    • Place of Presentation
      浜松
    • Year and Date
      2013-06-28
  • [Presentation] アロマターゼ阻害剤耐性機序と新規治療の可能性2013

    • Author(s)
      林慎一
    • Organizer
      第17回がん分子標的治療学会ランチョンセミナー
    • Place of Presentation
      京都
    • Year and Date
      2013-06-14
  • [Presentation] ホルモン療法耐性機序の多様性と新たな治療戦略2013

    • Author(s)
      林慎一
    • Organizer
      第25回日本内分泌外科学会総会シンポジウム
    • Place of Presentation
      山形
    • Year and Date
      2013-05-24
  • [Presentation] 閉経後進行・再発乳癌に対する薬物療法2013

    • Author(s)
      林慎一
    • Organizer
      Breast Cancer Scientific Exchange Meeting in Sendai
    • Place of Presentation
      仙台
    • Year and Date
      2013-05-14
  • [Presentation] 再発乳癌に対する新たな治療の可能性2013

    • Author(s)
      林慎一
    • Organizer
      Breast Cancer Round Meeting 2013
    • Place of Presentation
      仙台
    • Year and Date
      2013-04-05
  • [Presentation] 乳癌においてエストロゲンの制御を受けるFOX遺伝子2012

    • Author(s)
      稲葉綾香、花村徹、山口ゆり、林慎一
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121211-14
  • [Presentation] The androgen metabolite-dependent growth in hormone receptor positive breast cancer as a novel aromatase inhibitor-resistance mechanism2012

    • Author(s)
      Toru Hanamura, Toshifumi Niwa, Sayo Nishikawa, Hiromi Konno, Tatsuyuki Ghono, Yasuhito Kobayashi, Masafumi Kurosumi, Hiroyuki Takei, Yuri Yamaguchi, Ken-ichi Ito, Shin-ichi Hayashi
    • Organizer
      Annual San Antonio Breast Cancer Symposium
    • Place of Presentation
      San Antonio,USA
    • Year and Date
      20121204-08
  • [Presentation] Membrane-type Estrogen Receptor in Breast Cancer Cells Activated by Specific Ligands2012

    • Author(s)
      Toshifumi Niwa, Junko Takanobu, Yuri Shinagawa, Haruna Mori, Tatsuyuki Gohno, Yuri Yamaguchi, Takashi Suzuki, and Shin-ichi Hayashi
    • Organizer
      15^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Kanazawa,Japan
    • Year and Date
      20121115-17
  • [Presentation] Multiple Epigenetic Regulation Mechanism of CHIP Gene and Clinical Significance of Its Functional Re-expression Analysis in Breast Cancer2012

    • Author(s)
      Tatsuyuki Gohno, Fumihiko Suzuki, Toru Hanamura, Yuko Seino, Yuri Yamaguchi, Chika Tazawa, Toshifumi Niwa, Junn Yanagisawa, Shin-ichi Hayashi
    • Organizer
      15^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Kanazawa,Japan
    • Year and Date
      20121115-17
  • [Presentation] Estrogen Signal- Related Heterogeneity of Carcinoma-Associated Fibroblasts in Breast Cancer2012

    • Author(s)
      Yuri Yamaguchi, Hanako Oba, Kenichi Inoue, Tetsuji Suda, Yuko Seino, Hiroyuki Takei, Masafumi Kurosumi, Atsushi Mizokami, Shin-ichi Hayashi
    • Organizer
      15^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Kanazawa,Japan
    • Year and Date
      20121115-17
  • [Presentation] Heterogeneity of Luminal- type Breast Cancer and Cancer Stemness2012

    • Author(s)
      Takako Ito, Nozomi Sato, Chika Tazawa, Yuri Yamaguchi, Takuya Moriya, Hisashi Hirakawa, Shin-ichi Hayashi
    • Organizer
      15^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Kanazawa,Japan
    • Year and Date
      20121115-17
  • [Presentation] Individualization of Luminal-subtype Breast Cancer and Hormonal Therapy Resistance2012

    • Author(s)
      Shin-ichi Hayashi,Yuri Yamaguchi
    • Organizer
      15^<th> International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      Kanazawa,Japan
    • Year and Date
      20121115-17
  • [Presentation] 各種乳癌細胞株の癌幹細胞性の検討とサブタイプの可塑性2012

    • Author(s)
      佐藤望、伊藤貴子、田中美穂、田澤智香、山口ゆり、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] ホルモン療法耐性乳癌細胞におけるエストロゲンレセプターの発現低下とそのエピゲノム解析2012

    • Author(s)
      長友隆将、郷野辰幸、樋口徹、丹羽俊文、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 乳癌におけるエストロゲンレセプター(ER)α遺伝子のpromoter usageの意義.2012

    • Author(s)
      樋口徹、郷野辰幸、長友隆将、丹羽俊文、堀口淳、竹吉泉、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 乳癌幹細胞に対する癌微小環境の解析2012

    • Author(s)
      山口ゆり、須田哲司、黒住献、武井寛幸、黒住昌史、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 乳癌におけるCHIP遺伝子発現に関わるエピジェネティック制御機構の解析2012

    • Author(s)
      郷野辰幸、鈴木史彦、花村徹、清野祐子、山口ゆり、田澤智香、柳澤純、丹羽俊文、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 乳癌組織分離細胞の癌幹細胞性の検討2012

    • Author(s)
      伊藤貴子、佐藤望、田澤智香、山口ゆり、森谷卓也、平川久、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] ER陽性乳癌におけるエストロゲン依存性のFOXC1の発現2012

    • Author(s)
      稲葉綾香、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] 乳癌細胞膜型エストロゲン受容体に対するエストロゲンの配向性とERKの活性化2012

    • Author(s)
      高信純子、丹羽俊文、品川優理、郷野辰幸、山口ゆり、鈴木貴、林慎一
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] ER活性化能の異なる乳癌間質線維芽細胞が構築する癌微小環境の解析2012

    • Author(s)
      須田哲司、清野祐子、黒住献、武井寛幸、黒住昌史、林慎一、山口ゆり
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] ER遺伝子のPromoter Usage・エピゲノム制御とER陽性乳癌個別化2012

    • Author(s)
      樋口徹、郷野辰幸、長友隆将、堀口淳、竹吉泉、林慎一
    • Organizer
      第20回日本乳癌学会学術総会
    • Place of Presentation
      熊本
    • Year and Date
      20120628-30
  • [Presentation] ホルモン療法耐性細胞と癌幹細胞性の検討2012

    • Author(s)
      佐藤望、伊藤貴子、田中美穂、田澤智香、森谷卓也、平川久、山口ゆり、林慎一
    • Organizer
      第20回日本乳癌学会学術総会
    • Place of Presentation
      熊本
    • Year and Date
      20120628-30
  • [Presentation] Androgenシグナル抑制によるAI剤耐性機構2012

    • Author(s)
      花村徹、丹羽俊文、遠藤恵、郷野辰幸、山口ゆり、黒住昌史、武井寛幸、伊藤研一、林慎一
    • Organizer
      第20回日本乳癌学会学術総会
    • Place of Presentation
      熊本
    • Year and Date
      20120628-30
  • [Presentation] 癌幹細胞性によるLuminal型乳癌の新たな個別化2012

    • Author(s)
      伊藤貴子、佐藤望、田澤智香、山口ゆり、森谷卓也、平川久、林慎一
    • Organizer
      第20回日本乳癌学会学術総会
    • Place of Presentation
      熊本
    • Year and Date
      20120628-30
  • [Presentation] アロマターゼ阻害剤耐性機序の多様性と治療戦略の基礎2012

    • Author(s)
      林慎一
    • Organizer
      第20回日本乳癌学会学術総会
    • Place of Presentation
      熊本
    • Year and Date
      20120628-30
  • [Presentation] Individualization for Therapeutic Management of Luminal Subtype Breast Cancer2011

    • Author(s)
      Shin-ichi Hayashi, Yuri Yamaguchi
    • Organizer
      Grobal Breast Cancer Conference 2011
    • Place of Presentation
      Seoul,Korea
    • Year and Date
      20111006-08
  • [Presentation] エストロゲン枯渇耐性乳癌細胞株のER非依存的増殖におけるJNKの役割2011

    • Author(s)
      藤木夏、今野広海、郷野辰幸、山口ゆり、清野祐子、丹羽俊文、林慎一
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] レトロゾール耐性MCF-7におけるアロマターゼ非依存的なエストロゲン産生メカニズム2011

    • Author(s)
      遠藤恵、花村徹、郷野辰幸、丹羽俊文、林慎一
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-05
  • [Presentation] アンドロゲン代謝産物依存性増殖を示す乳癌細胞株の樹立と新たなアロマターゼ阻害薬耐性機序の検討2011

    • Author(s)
      花村徹、丹羽俊文、西川紗世、今野広海、郷野辰幸、田澤智香、山口ゆり、伊藤研一、林慎一
    • Organizer
      第19回日本乳癌学会学術総会
    • Place of Presentation
      仙台
    • Year and Date
      20110902-04
  • [Presentation] ER陽性乳癌のホルモン療法耐性獲得機序とその克服2011

    • Author(s)
      林慎一
    • Organizer
      第8回日本乳癌学会関東地方会
    • Place of Presentation
      大宮(特別講演)
    • Year and Date
      2011-12-03
  • [Patent(Industrial Property Rights)] アンドロゲンレセプター依存性乳癌細胞株の作成方法、該当細胞株を用いたスクリーニング方法、ならびに乳癌患者におけるアンドロゲンレセプター依存性獲得の判定方法、キット及びマーカー2013

    • Inventor(s)
      林 慎一、藤井里圭
    • Industrial Property Rights Holder
      東北大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-108774
    • Filing Date
      2013-05-23
    • Overseas
  • [Patent(Industrial Property Rights)] ホルモン療法耐性乳癌細胞株及びそれを用いた薬剤スクリーニング方法2011

    • Inventor(s)
      林慎一
    • Industrial Property Rights Holder
      東北大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2011-152458
    • Filing Date
      2011-07-11
    • Overseas

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Published: 2015-07-16  

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