Analysis of estrogen signaling specific and/or common to brainfunction and cancer, and its clinical relevance

• Project/Area Number: 22591016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Saitama Medical University
• Principal Investigator: IKEDA Kazuhiro 埼玉医科大学, 医学部, 講師 (30343461)
• Research Collaborator: INOUE Satoshi 埼玉医科大学, 医学部, 客員教授 (40251251)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エストロゲン / 脳 / がん / 転写 / 遺伝子 / 乳がん

Research Abstract

Estrogen plays important roles in brain function and breast cancer. In this study, I aimed to explore the novel estrogen-responsive genes in brain and cancer tissues for identifying specific and/or common estrogen signaling pathway between these tissues. In addition to estrogen-responsive genes that we have previously reported, clinical relevance of these estrogen-responsive genes is also explored. We identified novelestrogen-responsive genes specific in hippocampus, hypothalamus and brain stem. These novel estrogen-responsive genes are known to be associated with breast cancer. We also demonstrated that the expression of transcription factors, FOXA1 and FOXP1 is induced by estrogen in breast cancer cells and immunoreactivities of FOXA1 and FOXP1 are positively correlated with good prognosis of breast cancer patients with tamoxifen treatment. These findings would uncover novel role of estrogen signaling in brain function and cancers.

Research Products

• [Journal Article] A-sequencing of MCF-7 breast cancer cells identifies novel estrogen-responsive genes with functional estrogen receptor-binding sites in the vicinity of their transcription start sites (2013)
  • Author(s): Yamaga R, Ikeda K, Horie-Inoue K, Ouchi Y, Suzuki Y, Inoue S
  • Journal Title: Horm Cancer (in press) Volume: 4 Issue: 4 Pages: 222-232
  • DOI: 10.1007/s12672-013-0140-3
  • Peer Reviewed
• [Journal Article] Expression and regulation of transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in human endometrium (2013)
  • Author(s): Hiroi H
  • Journal Title: Mol Cell Endocrinol Volume: 365 Issue: 2 Pages: 146-152
  • DOI: 10.1016/j.mce.2012.10.015
  • Peer Reviewed
• [Journal Article] Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice (2012)
  • Author(s): Ikeda K, Tsukui T, Imazawa Y, Horie-Inoue K, Inoue S
  • Journal Title: Biochem Biophys Res Commun Volume: 425 Issue: 4 Pages: 912-917
  • DOI: 10.1016/j.bbrc.2012.07.170
  • Peer Reviewed
• [Journal Article] Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells (2012)
  • Author(s): Abe Y, Ijichi N, Ikeda K, Kayano H, Horie-Inoue K, Takeda S, Inoue S
  • Journal Title: Cancer Sci Volume: 103 Issue: 4 Pages: 806-812
  • DOI: 10.1111/j.1349-7006.2012.02201.x
  • Peer Reviewed
• [Journal Article] TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer (2012)
  • Author(s): Takayama K, Horie-Inoue K, Suzuki T, Urano T, Ikeda K, Fujimura T, Takahashi S, Homma Y, Ouchi Y, Inoue S
  • Journal Title: Mol Endocrinol Volume: (in press) Issue: 5 Pages: 748-761
  • DOI: 10.1210/me.2011-1242
  • Peer Reviewed
• [Journal Article] Conditional expression of human bone Gla protein in osteoblasts causes skeletal abnormality in mice (2012)
  • Author(s): Ikeda K, Tsukui T, Tanaka D, Maruyama Y, Horie-Inoue K, Inoue S
  • Journal Title: Biochem Biophys Res Commun Volume: 424 Issue: 1 Pages: 164-169
  • DOI: 10.1016/j.bbrc.2012.06.098
  • Peer Reviewed
• [Journal Article] Association of double-positive FOXA1 and FOXP1 immunoreactivities with favorable prognosis of tamoxifen-treated breast cancer patients (2012)
  • Author(s): Ijichi N, Shigekawa T, Ikeda K,Horie-Inoue K, Shimizu C, Saji S, Aogi K, Tsuda H, Osaki A, Saeki T, Inoue S
  • Journal Title: Horm Cancer Volume: 3 Issue: 4 Pages: 147-159
  • DOI: 10.1007/s12672-012-0111-0
  • Peer Reviewed
• [Journal Article] Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer (2012)
  • Author(s): Obinata D, Takayama K, Urano T, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: Int J Cancer Volume: 130 Issue: 5 Pages: 1021-1028
  • DOI: 10.1002/ijc.26043
  • Peer Reviewed
• [Journal Article] ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration (2012)
  • Author(s): Obinata D, Takayama K, Urano T, Murata T, Ikeda K, Horie-Inoue K, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: Int J Cancer Volume: 130 Issue: 10 Pages: 2240-2248
  • DOI: 10.1002/ijc.26224
  • NAID: 10031156601
  • Peer Reviewed
• [Journal Article] Terf/TRIM17 stimulates degradation of kinetochore protein ZWINT and regulates cell proliferation (2012)
  • Author(s): Endo H
  • Journal Title: J.Biochem. Volume: 151 Pages: 139-144
  • Peer Reviewed
• [Journal Article] Conditional expression of constitutively active estrogen receptor α in osteoblasts increases bone mineral density in mice (2011)
  • Author(s): Ikeda K, Tsukui T, Horie-Inoue K, Inoue S
  • Journal Title: FEBS Let Volume: 585 Issue: 9 Pages: 1303-1309
  • DOI: 10.1016/j.febslet.2011.03.038
  • Peer Reviewed
• [Journal Article] FOXP1, an estrogen-inducible transcription factor, modulates cell proliferation in breast cancer cells and 5-year recurrence-free survival of patients with tamoxifen-treated breast cancer (2011)
  • Author(s): Shigekawa T, Ijichi N, Ikeda K, Horie-Inoue K, Shimizu C, Saji S, Aogi K, Tsuda H, Osaki A, Saeki T, Inoue S
  • Journal Title: Horm Cancer Volume: 2 Issue: 5 Pages: 286-297
  • DOI: 10.1007/s12672-011-0082-6
  • Peer Reviewed
• [Journal Article] Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer (2011)
  • Author(s): Ijichi N, Shigekawa T, Ikeda K, Horie-Inoue K, Fujimura T, Tsuda H, Osaki A, Saeki T, Inoue S
  • Journal Title: J Steroid Biochem Mol Biol Volume: 123 Issue: 1-2 Pages: 1-7
  • DOI: 10.1016/j.jsbmb.2010.09.002
  • Peer Reviewed
• [Journal Article] Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer (2011)
  • Author(s): Oyama M, Nagashima T, Suzuki T, Kozuka-Hata H, Yumoto N, Shiraishi Y, Ikeda K, Kuroki Y, Gotoh N, Ishida T, Inoue S, Kitano H, Okada-Hatakeyama M.
  • Journal Title: J Biol Chem Volume: 286 (1) Issue: 1 Pages: 818-29
  • DOI: 10.1074/jbc.m110.156877
  • Peer Reviewed
• [Journal Article] Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells (2011)
  • Author(s): Takayama K, Tsutsumi S, Katayama S, Okayama T, Horie-Inoue K, Ikeda K, Urano T, Kawazu C, Hasegawa A, Ikeo K, Gojyobori T, Ouchi Y, Hayashizaki Y, Aburatani H, Inoue S
  • Journal Title: Oncogene Volume: 30 Issue: 5 Pages: 619-630
  • DOI: 10.1038/onc.2010.436
  • Peer Reviewed
• [Journal Article] Conditional expression of constitutively active estrogen receptor α in osteoblasts increases bone mineral density in mice (2011)
  • Author(s): Ikeda K
  • Journal Title: FEBS Lett Volume: 585 Pages: 1303-1309
  • Peer Reviewed
• [Journal Article] Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer (2011)
  • Author(s): Oyama M
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 818-829
  • Peer Reviewed
• [Journal Article] Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer (2011)
  • Author(s): Ijichi N
  • Journal Title: The Journal of Steroid Biochemistry and Molecular Biology Volume: 123 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Knock-down of Efp by DNA-modified small interfering RNA inhibits breast cancer cell proliferation and in vivo tumor growth (2010)
  • Author(s): Ueyama K, Ikeda K, Sato W, Nakasato N, Horie-Inoue K, Takeda S, Inoue S
  • Journal Title: Cancer Gene Ther Volume: 17 Issue: 9 Pages: 624-632
  • DOI: 10.1038/cgt.2010.19
  • Peer Reviewed
• [Journal Article] Knock-down of Efp by DNA-modified small interfering RNA inhibits breast cancer cell proliferation and in vivo tumor growth (2010)
  • Author(s): Ueyama K
  • Journal Title: Cancer Gene Therapy Volume: 17 Pages: 624-632
  • Peer Reviewed
• [Presentation] 前立腺がん細胞における内分泌療法耐性獲得に関与するマイクロ RNA の探索 (2012)
  • Author(s): 池田和博 、宮崎利明、堀江公仁子、岡本康司、井上聡
  • Organizer: 第20回日本ステロイドホルモン学会
  • Place of Presentation: 石川市
  • Year and Date: 2012-11-18
• [Presentation] Cytochrome c oxidase subunit 7 related protein はミトコンドリアの呼吸活性を制御し、生体におけるエネルギー代謝に関与する (2012)
  • Author(s): 池田和博、堀江公仁子、井上聡
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市
• [Presentation] MicroRNA profiling of tamoxifen-sensitive and -resistant breast cancer MCF-7 cells analyzed by deep sequencing (2012)
  • Author(s): Ikeda K, Horie-Inoue K, Mano H, Inoue S
  • Organizer: 15th International Congress on Hormonal Steroids and Hormones & Cancer
  • Place of Presentation: Ishikawa, Japan
• [Presentation] マイクロRNAを介する乳がん細胞の内分泌治療抵抗性の制御 (2012)
  • Author(s): 池田和博
  • Organizer: 第4回日本RNAi研究会
  • Place of Presentation: グランドプリンスホテル広島（広島市）
• [Presentation] フォークヘッド転写因子FOXP1の全ゲノムにおける結合部位同定によるERシグナル調節機構の解析 (2012)
  • Author(s): 伊地知暢広
  • Organizer: 第20回日本ステロイドホルモン学会
  • Place of Presentation: 石川県立音楽堂（金沢市）
• [Presentation] Knockdown of Efp DNA-modified small interfering RNA inhibits breast and uterine cancer cell proliferation (2012)
  • Author(s): Kazuhiro Ikeda
  • Organizer: keystone symposium : Nucleic Acid Therapeutics : From Base Pairs to Bedsides
  • Place of Presentation: Eldorado Hotel & Spa (Santa Fe, NM, USA)
• [Presentation] 乳がん細胞における全ゲノムレベルでのエストロゲン応答性転写開始点の探索と応答因子の機能解析 (2011)
  • Author(s): 池田和博、山賀亮之介、堀江公仁子、 井上聡
  • Organizer: 第19回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2011-11-26
• [Presentation] 乳がんならびに子宮内膜がんにおけるフォークヘッド転写因子 FOXA1 の機能と臨床的意義 (2011)
  • Author(s): 伊地知暢広、重川崇、阿部弥生、 池田和博、堀江公仁子、茅野秀一、津田均、大崎昭彦、竹田省、佐伯俊昭、井上聡
  • Organizer: 第19回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2011-11-26
• [Presentation] 乳がん細胞における全ゲノムレベルでのエストロゲン応答性転写開始点の探索と応答因子の機能解析 (2011)
  • Author(s): 池田和博
  • Organizer: 第19回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡大学医学部メディカルホール(福岡市)
  • Year and Date: 2011-11-26
• [Presentation] 乳がんならびに子宮内膜がんにおけるフォークヘッド転写因子FOXA1の機能と臨床的意義 (2011)
  • Author(s): 伊地知暢広
  • Organizer: 第19回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡大学医学部メディカルホール(福岡市)
  • Year and Date: 2011-11-26
• [Presentation] 子宮内膜癌におけるFOXA1の発現は予後良好因子に関連する (2011)
  • Author(s): 阿部弥生
  • Organizer: 第11回関東ホルモンと癌研究会
  • Place of Presentation: 持田製薬株式会社本社ルークホール(東京都)
  • Year and Date: 2011-01-29
• [Presentation] Estrogen-dependent transcriptome analysis in breast cancer MCF-7 cells by RNA-sequencing (2011)
  • Author(s): Ikeda K, Yamaga R, Horie-Inoue K, Suzuki Y, Inoue S
  • Organizer: EMBO Conference, Nuclear Receptors
  • Place of Presentation: Sitges, Barcelona, Spain
• [Presentation] 活性型エストロゲン受容体はコンディショナルトランスジェニックマウスの骨芽細胞ならびに軟骨細胞において異なる in vivo 作用を示す (2011)
  • Author(s): 池田和博、堀江公仁子、 井上聡
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 大阪市
• [Presentation] 子宮内膜癌におけるFOXA1のエストロゲン応答性と臨床病理解析 (2011)
  • Author(s): 阿部弥生
  • Organizer: 第84回日本内分泌学会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
• [Presentation] 活性型エストロゲン受容体はコンディショナルトランスジェニックマウスの骨芽細胞ならびに軟骨細胞において異なるin vivo作用を示す (2011)
  • Author(s): 池田和博
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪市)
• [Presentation] Cytochrome c oxidase subunit 7a related polypeptide COX7RP is an estrogen target gene that plays a role in the OXPHOS pathway (2011)
  • Author(s): Kazuhiro Ikeda
  • Organizer: 8th Conference of Asian Society for Mitochondrial Research and Medicine
  • Place of Presentation: Kagoshima Citizens' Culture Hall (Kagoshima, Japan)
• [Presentation] Estrogen-dependent transcriptome analysis in breast cancer MCF-7 cells by RNA-sequencing (2011)
  • Author(s): Kazuhiro Ikeda
  • Organizer: EMBO Conference NUCLEAR RECEPTORS
  • Place of Presentation: Hotel Melia Sitges (Sitges, Spain)
• [Presentation] An estrogen-inducible transcription factor FOXP1 promotes estrogen-dependent cell proliferation of breast cancer cells and is associated with 5-year disease-free survival in patients with tamoxifen-treated breast cancer (2011)
  • Author(s): Takashi Shigekawa
  • Organizer: 34th Annual San Antonio Breast Cancer Symposium
  • Place of Presentation: Henry B.Gonzalez Convention Center (San Antonio, TX, USA)
• [Presentation] 活性型エストロゲン受容体を軟骨細胞で発現するトランスジェニックマウスの解析 (2010)
  • Author(s): 池田和博、津久井通、堀江公仁子、 井上聡
  • Organizer: 第18回日本ステロイドホルモン学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-11-27
• [Presentation] エストロゲン関連受容体 ERRg は乳がんにおける細胞増殖とエストロゲンシグナル経路を調節する (2010)
  • Author(s): 伊地知暢広、重川崇、 池田和博、堀江公仁子、津田均、大崎昭彦、佐伯俊昭、井上聡
  • Organizer: 第18回日本ステロイドホルモン学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-11-27
• [Presentation] ステロイドホルモン学会活性型エストロゲン受容体を軟骨細胞で発現するトランスジェニックマウスの解析 (2010)
  • Author(s): 池田和博
  • Organizer: 第18回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 愛知県産業労働センター(名古屋市)
  • Year and Date: 2010-11-27
• [Presentation] フォークヘッド転写因子FOXP1は乳癌においてエストロゲンシグナル調節に関与する (2010)
  • Author(s): 重川崇
  • Organizer: 第18回 日本乳癌学会学術総会
  • Place of Presentation: ロイトン札幌(札幌市)
  • Year and Date: 2010-06-24
• [Presentation] 骨芽細胞において活性型エストロゲン受容体を過剰発現するマウスは骨密度の増加を示す (2010)
  • Author(s): 池田和博、津久井通、堀江公仁子、 井上聡
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
• [Presentation] Altered hormonal regulation of gene expression in anti-hormone drug-resistant and hormone-deprived breast and prostate cancer cell (2010)
  • Author(s): Horie-Inoue K
  • Organizer: The 92th Annual meeting of Endocrine Society (ENDO2010)
  • Place of Presentation: San Diego Convention Center (San Diego, CA)
• [Presentation] 骨芽細胞において活性型エストロゲン受容体を過剰発現するマウスは骨密度の増加を示す (2010)
  • Author(s): 池田和博
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸ポートアイランド(神戸市)
• [Presentation] Integrative analysis of phosphoproteome and transcriptome dynamics defines drug-resistance properties of breast cancer (2010)
  • Author(s): 尾山大明
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸ポートアイランド(神戸市)
• [Remarks]
  • URL: http://www.saitama-med.ac.jp/genome/Div02_GRST/index.html