Molecular mechanism of difference of estrogen sensitivity and response to endocrine therapy in breast and endometrial cancers

2009 Fiscal Year Final Research Report

• Project/Area Number: 19591071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Tohoku University
• Principal Investigator: HAYASHI Shin-ichi Tohoku University, 大学院・医学系研究科, 教授 (60144862)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Yuri 埼玉県立がんセンター, 臨床腫瘍研究所, 主任研究員 (80166628)
• Project Period (FY): 2007 – 2009
• Keywords: 子宮内膜癌 / 乳癌 / エストロゲン / マイクロアレイ / ホルモン療法 / 核内受容体

Research Abstract

Microarray analysis of the breast and endometrial cancer revealed that the expression profile of their ER-response genes was significantly different from each others. The cancer microenvironment of the endometrial cancer showed ER activating ability as similar to that in breast cancer. Furthermore, endometrial cancer cells obtained from surgical specimens showed substantial ER activity by ERE-GFP adenovirus assay. These results suggest that aromatase inhibitor may have some therapeutic value in some endometrial cancers.

Research Products

• [Journal Article] Estrogen-related cancer microenvironment of breast carcinoma (2009)
  • Author(s): Yamaguchi, Y.,Hayashi, S.
  • Journal Title: Endocrine J. 56(1) Pages: 1-7
  • Peer Reviewed
• [Journal Article] Loss of estrogen receptor b isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epitherial ovarian carcinoma (2008)
  • Author(s): Suzuki, F., Akahira, J., Miura, I., Suzuki, T., Ito, K., Hayashi, S., Sasano, H., Yaegashi, N.
  • Journal Title: Cancer Sci. 99 Pages: 2365-2372
  • Peer Reviewed
• [Journal Article] Estrogen signaling pathway and hormonal therapy (2008)
  • Author(s): Hayashi, S., Yamaguchi, Y.
  • Journal Title: Breast Cancer 15 Pages: 256-261
  • Peer Reviewed
• [Journal Article] Adaptation to estradiol deprivation causes up-regulation of growth factor pathways and hypersensitivity to estradiol in breast cancer cells (2008)
  • Author(s): Santen RJ, Song RX, Masamura S, Yue W, Fan P, Sogon T, Hayashi S, Nakachi K, Eguchi H.
  • Journal Title: Adv.Exp.Med.Biol. 630 Pages: 19-34
  • Peer Reviewed
• [Journal Article] Intratumoral Estrogens and Estrogen Receptors in Human Non-Small Cell Lung Carcinoma (2008)
  • Author(s): Niikawa H, Suzuki T, Miki Y, Suzuki S, Nagasaki S, Akahira J, Honma S, Evans DB, Hayashi S, Kondo T, Sasano H.
  • Journal Title: Clin Cancer Res. 14 Pages: 4417-4426
  • Peer Reviewed
• [Journal Article] Estrogen signaling in cancer microenvironment and prediction of response to hormonal therapy (2008)
  • Author(s): Hayashi, S., Yamaguchi, Y.
  • Journal Title: J.Steroid Biochem.Mol.Biol. 109 Pages: 201-206
  • Peer Reviewed
• [Journal Article] Midkine and its clinical significance in endometrial cancer (2008)
  • Author(s): Tanabe, K., Matsumoto, M., Ikematsu, S., Nagase, S., Hatakeyama, A., Takano, T., Niikura, H., Ito, K., Kadomatsu, K., Hayashi, S., Yaegashi, N.
  • Journal Title: Cancer Sci. 99 Pages: 267-271
  • Peer Reviewed
• [Journal Article] Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction (2008)
  • Author(s): Matsumoto, M., Yamaguchi, Y., Seino, Y., Hatakeyama, A., Takei, H., Niikura, H., Ito, K., Suzuki, T., Sasano, H., Yaegashi, N. Hayashi, S.
  • Journal Title: Endocrine-Related Cancer 15 Pages: 451-463
  • Peer Reviewed
• [Journal Article] The expression of retinoic acid receptors in human endometrial carcinoma (2008)
  • Author(s): Tanabe, K., Utsunomiya, H., Tamura, M., Niikura, H., Takano, T., Yoshinaga, K., Nagase, S., Suzuki, T., Ito, K., Matsumoto, M., Hayashi, S. Yaegashi, N.
  • Journal Title: Cancer Sci. 99 Pages: 1125-1130
  • Peer Reviewed
• [Journal Article] Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer (2007)
  • Author(s): Mita, K., Zhang, Z., Ando, Y., Toyama, T., Hamaguchi, M., Kobayashi, S., Hayashi, S., Fujii, Y., Iwase, H. Yamashita, H.
  • Journal Title: Jpn.J.Clin.Oncol. 37(8) Pages: 575-582
  • Peer Reviewed
• [Journal Article] Early growth responsive gene 3 (EGR3) in human breast carcinoma : a regulator of estrogen-mediated invasion and a potent prognostic factor (2007)
  • Author(s): Suzuki, T., Inoue, A., Miki, Y., Moriya T., Ishida, T., Hirakawa, H., Yamaguchi, Y., Hayashi, S. Sasano, H.
  • Journal Title: Endocrine-Related Cancer 14 Pages: 279-292
  • Peer Reviewed
• [Journal Article] Aromatase localization in human breast cancer tissues-possible interaction between intratumoral stromal and parenchymal cells (2007)
  • Author(s): Miki, Y., Suzuki, T., Tazawa C., Yamaguchi, Y., Kitada, K., Honma, S., Moriya, T., Hirakawa, H., Evans, D.B., Hayashi, S., Ohuchi, N. Sasano, H.
  • Journal Title: Cancer Res. 67(8) Pages: 3945-3954
  • Peer Reviewed
• [Journal Article] Demethylation of promoter C region of estrogen receptor α gene is correlated with its enhanced expression in estrogen-ablation resistant MCF-7 cells (2007)
  • Author(s): Sogon, T., Masamura, S., Hayashi, S., Santene, R.J., Nakachi, K., Eguchi, H.
  • Journal Title: J.Steroid Biochem.Mol.Biol. 105 Pages: 106-114
  • Peer Reviewed
• [Journal Article] Comparative profilimg of the gene expression for estrogen responsiveness in cultured human cell lines (2007)
  • Author(s): Inoue, A., Seino, Y., Terasaka, S., Hayashi, S., Yamori, T., Tanji, M. Kiyama, R.
  • Journal Title: Toxicology In Vitro 21 Pages: 741-752
  • Peer Reviewed
• [Journal Article] 5・-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production (2007)
  • Author(s): Suzuki, T., Miki, Y., Moriya, T., Akahira, J., Ishida, T., Hirakawa, H., Yamaguchi, Y., Hayashi, S. Sasano, H.
  • Journal Title: Int.J.Cancer 120 Pages: 285-291
  • Peer Reviewed
• [Presentation] Antitumor activity of chemoendocrime therapy in premenopasual (Capecitabine [CAP]+Tamoxifen[TAM]) and postmenopausal (CAP+Letrozole[LET]) human breast cancer [BC] xenograft models (2008)
  • Author(s): Motoyuki Kataoka, Yuri Yamaguchi, Noriaki Sawada, Yo-ichiro Morita, Dean B Evans, Hideyuki Yasuno, Kazushige Mori, Shin-ichi Hayashi
  • Organizer: 31st San Antonio Breast Cancer Cymposium
  • Place of Presentation: San Antonio
  • Year and Date: 2008-12-11
• [Presentation] ユビキチンリガーゼCHIPは癌の浸潤性を抑制する (2008)
  • Author(s): 神代理史, 相馬佳絵, 村山明子, 仲島由佳, 藤村亜紀子, 大家祥平, 山口ゆり, 川野輪香織, 木村圭志, 黒住昌史, 林慎一, 柳澤純
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 乳癌のエストロゲンシグナルと Cancer-Associated Fibroblast(CAF) の機能 (2008)
  • Author(s): 山口ゆり, 松本光代, 大庭華子, 清野祐子, 武井寛幸, 黒住昌史, 林慎一
  • Organizer: 第16回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福井
  • Year and Date: 2008-11-22
• [Presentation] Association of Estrogen Receptor α and HDAC6 causes novel nongenomic action in breast cancer cells (2008)
  • Author(s): Kotaro Azuma, Tomohiko Urano, Shin-ichi Hayashi, Ryuichi Sakai, Yasuyoshi Ouchi, Satoshi Inoue
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 乳癌のエストロゲンシグナルに関わる間質線維芽細胞の特性の解析 (2008)
  • Author(s): 大庭華子, 清野祐子, 小林康人, 武井寛幸, 黒住昌史, 林慎一, 山口ゆり
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 乳癌微小環境のエストロゲンシグナルに対する Chemo-endocrine 併用療法による抑制効果 (2008)
  • Author(s): 山口ゆり, 清野祐子, 林慎一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] ERのリガンド非依存性活性化を呈するエストロゲン枯渇耐性乳癌細胞株の樹立 (2008)
  • Author(s): 今野広海, 白山知子, 山口ゆり, 清野祐子, 松本光代, 丹羽俊文, 林慎一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] ERE-GFPアッセイによる原発性乳がんのエストロゲン受容体転写解析とその臨床病理 (2008)
  • Author(s): 松本光代, 清野祐子, 山口ゆり, 武井寛幸, 黒住昌史, 八重樫伸生, 林慎一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] In vivo assessment of estrogen signal-related function of carcinoma-associated fibroblast (CAF) in human breast cancer (2008)
  • Author(s): Yamaguchi, Y., Seino, Y., Oba, H., Takei, H., Kurosumi, M., Hayashi, S.
  • Organizer: 13th International Congress on Hormonal Steroids and Hormones & Cancer
  • Place of Presentation: ケベック
  • Year and Date: 2008-09-27
• [Presentation] 子宮体癌-間質細胞におけるエストロゲンを介した相互作用の解析 (2008)
  • Author(s): 松本光代, 伊藤潔, 新倉仁, 笹野公伸, 八重樫, 伸生林慎一
  • Organizer: 第13回日本産婦人科乳癌学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-14
• [Presentation] ERE-GFPアッセイを用いた原発性乳癌のエストロゲン受容体転写活性解析と臨床病理学的因子との関連 (2008)
  • Author(s): 松本光代, 清野祐子, 山口ゆり, 武井寛幸, 黒住昌史, 八重樫伸生, 林慎一
  • Organizer: 第9回ホルモンと癌研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2008-06-20
• [Presentation] ヒト上皮性卵巣癌における Estrogen receptor beta isoforms の発現とメチル化についての検討 (2008)
  • Author(s): 鈴木史彦, 赤平純一, 三浦伊久美, 伊藤潔, 鈴木貴, 林慎一, 笹野公伸, 八重樫伸生
  • Organizer: 第9回ホルモンと癌研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2008-06-20
• [Presentation] ERの恒常的活性化を呈するホルモン療法耐性モデル乳癌細胞株の樹立 (2008)
  • Author(s): 今野広海, 白山知子, 山口ゆり, 清野祐子, 松本光代, 丹羽俊文, 林慎一
  • Organizer: 第9回ホルモンと癌研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2008-06-20
• [Presentation] エストロゲンシグナルに関連した乳癌間質細胞の特性の解析 (2008)
  • Author(s): 大庭華子, 山口ゆり, 小林康人, 武井寛幸, 黒住昌史, 林慎一
  • Organizer: 第9回ホルモンと癌研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2008-06-20
• [Presentation] 乳癌における細胞膜局在エストロゲン受容体の新規核外作用の解析 (2008)
  • Author(s): 東浩太郎, 堀江公仁子, 大内尉義, 林慎一, 堺隆一, 井上聡
  • Organizer: 第4回SERM学術研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-15
• [Presentation] Rationale for salvage therapy with high-dose Selective Estrogen Receptor Modulator after treatment failure of Aromatase Inhibitors in breast cancer (2008)
  • Author(s): S Saji, M Hirose, H Iwase, Y Yamaguchi, M Toi, S Hayashi, K Kuroi
  • Organizer: AMERICAN SOCIETY OF CLINICAL ONCOLOGY
  • Place of Presentation: Chicago
  • Year and Date: 2008-05-30
• [Presentation] Expression of estrogen receptor(ER) beta isoforms and its correlation with DNA methylation in human epithelial ovarian cancer (2008)
  • Author(s): F Suzuki, J Akahira, I Miura, S Nagase, T Takano, H Niikura, T Suzuki, K Ito, S Hayashi, H Sasano, N Yaegashi
  • Organizer: AMERICAN SOCIETY OF CLINICAL ONCOLOGY
  • Place of Presentation: Chicago
  • Year and Date: 2008-05-30
• [Presentation] ヒト上皮性卵巣癌における Estrogen receptor beta isoforms の発現とメチル化についての検討 (2008)
  • Author(s): 鈴木史彦, 赤平純一, 伊藤潔, 鈴木貴, 林慎一, 笹野公伸, 八重樫伸生
  • Organizer: 第81回日本内分泌学会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] ERE-GFPアッセイによる原発性乳癌のエストロゲン受容体転写活性の解析と臨床病理学的因子との関連 (2008)
  • Author(s): 松本光代, 清野祐子, 山口ゆり, 武井寛幸, 黒住昌史, 笹野公伸, 八重樫伸生, 林慎一
  • Organizer: 第16回日本内分泌学会東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2008-04-26
• [Presentation] ユビキチンリガーゼCHIPは癌の悪性化を抑制する (2008)
  • Author(s): 神代理史, 相馬佳絵, 中島由佳, 山口ゆり, 川野輪香織, 木村圭志, 黒住昌史, 林慎一, 柳澤純
  • Organizer: 第8回関東ホルモンと癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-01-29
• [Book] みんなに役立つ乳癌の基礎と臨床 (2009)
  • Author(s): 林慎一
  • Total Pages: 53-63
  • Publisher: 医薬ジャーナル株式会社
• [Patent(Industrial Property Rights)] A transgenic cell and method for cell analysis (2008)
  • Inventor(s): 林慎一, 山口ゆり
  • Industrial Property Rights Holder: オリンパス株式会社
  • Industrial Property Number: 特許06756855-1222PCT/JP2006310935
  • Filing Date: 2008-02-08
  • Overseas