Epigenetic analysis of aromatase gene toward the advanced early diagnostics in endometriosis

• Project/Area Number: 22591824
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tottori University
• Principal Investigator: IZAWA Masao 鳥取大学, 医学部, 特任教授 (50032222)
• Co-Investigator(Kenkyū-buntansha): HARADA Tasuku 鳥取大学, 医学部, 教授 (40218649) ; 谷口 文紀 鳥取大学, 医学部附属病院, 講師 (40322218)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 子宮内膜症 / エストロゲン産生異常 / アロマターゼ遺伝子 / CpGアイランド / DNAメチル化 / エピゲノム異常 / 早期診断分子マーカー / CpG配列 / アロマターゼ / 網羅的DNAメチル化解析 / 子宮内膜症特異的メチル化CpG / 早期診断分子マーカ / 早期診断法

Research Abstract

A marked up-regulation of aromatase gene leading to a high estrogen environment in endometriotic tissues has been suggested as the aberrant DNA methylation (Izawa et al. 2008). The observation further suggested the aberrant genome-wide DNA methylation in endometriosis. Toward the advanced early diagnostics in endometriosis, we challenged a genome-wide extraction of aberrant DNA methylation along with the epigenetic analysis of aromatase gene. We finally extracted approximately 1800 GpG sites as the candidates for early diagnostic markers in endometriosis. Case studies are under way toward the final extraction of these candidates.

Research Products

• [Journal Article] The cellular inhibitor of apoptosis protein-2 is a possible target of novel treatment for endometriosis (2014)
  • Author(s): Taniguchi F, Higaki H, Izawa M, Azuma Y, Hirakawa E, Deura I, Iwabe T, Hata K and Harada T
  • Journal Title: American Journal of Reproductive endocrinology Volume: 71 Pages: 278-285
  • Peer Reviewed
• [Journal Article] The cellular inhibitor of apoptosis protein-2 is a possible target of novel treatment for endometriosis (2014)
  • Author(s): Taniguchi F, Higaki H, Izawa M, Azuma Y, Deura I, Iwabe T,Hata K, Harada T.
  • Journal Title: American Journal of Reproductive Immunology Volume: 71 Pages: 278-285
  • Peer Reviewed
• [Journal Article] Epigenetic aberration of gene expression in endometriosis (2013)
  • Author(s): Izawa M, Taniguchi F, Terakawa N and Harada T
  • Journal Title: Frontiers in Bioscience (Elite Ed) Volume: 5 Pages: 900-910
  • Peer Reviewed
• [Journal Article] Epigenetic aberration of gene expression in endometriosis (2013)
  • Author(s): Izawa M, Taniguchi F, Terakawa N, Harada T.
  • Journal Title: Frontiers in Bioscience (Elite Ed) Volume: 5 Pages: 900-9100
  • Peer Reviewed
• [Journal Article] 子宮内膜症におけるアロマターゼ遺伝子発現とエピジェネティック制御 (2012)
  • Author(s): 伊澤正郎,谷口文紀、寺川直樹、原田省
  • Journal Title: 日本エンドメトリオーシス学会誌 Volume: 33 Pages: 103-105
• [Journal Article] Genome-wide profiling of DNA methylation in endometriotic cells (2012)
  • Author(s): Izawa M, Taniguchi F, Terakawa N and Harada T
  • Journal Title: Journal of Endometriosis Volume: 4 Pages: 147-147
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of DNA methylation in endometriotic cells (2012)
  • Author(s): Izawa M, Taniguchi F, Harada T.
  • Journal Title: Journal of Endometriosis Volume: 4 Pages: 147-147
  • Peer Reviewed
• [Journal Article] Demethylation of a promoter-distal CpG island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues (2011)
  • Author(s): Izawa M, Taniguchi F, Uegaki T, Takai E, Iwabe T, Terakawa N and Harada T
  • Journal Title: Fetil Steril Volume: 95 Pages: 33-39
  • Peer Reviewed
• [Journal Article] Apoptosis and endometriosis (2011)
  • Author(s): Taniguchi F, Kaponis A, Izawa M, Kiyama T, Deura I, Ito M, Iwabe T, Adonakis G, Terakawa N and Harada T
  • Journal Title: Frontiers in Bioscience Volume: 3 Pages: 648-662
  • Peer Reviewed
• [Journal Article] Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues. (2011)
  • Author(s): Izawa M
  • Journal Title: Fertility and Sterility Volume: 95 Pages: 33-39
  • Peer Reviewed
• [Journal Article] Apoptosis and endometriosis. (2011)
  • Author(s): Izawa M
  • Journal Title: Frontiers in Bioscience Volume: 3 Pages: 648-662
  • Peer Reviewed
• [Journal Article] Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues (2011)
  • Author(s): Izawa M, 他5名
  • Journal Title: Fertility and Sterility (Epub 2010 Jul 23) Volume: 95 Pages: 33-39
  • Peer Reviewed
• [Presentation] 子宮内膜症におけるアロマターゼ発現とエピゲノム異常 (2013)
  • Author(s): 伊澤正郎、谷口文紀、原田省
  • Organizer: 第86回日本生化学会シンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 2013-09-13
• [Presentation] DNA methylation profiles associated with aberrant gene expressions in endometriosis (2013)
  • Author(s): Izawa M, Taniguchi F, Terakawa N and Harada T
  • Organizer: The Endocrine Society Annual Meeting & Expo
  • Place of Presentation: San Francisco
  • Year and Date: 2013-06-17
• [Presentation] Parthenoide reduces cell proliferation and PGE2 synthesis in human endometriotic stromal cells and inhibits development of endometriosis in murine model (2013)
  • Author(s): Taniguchi F, Takai E, Izawa M, Terakawa N and Harada T
  • Organizer: The Endocrine Society Annual Meeting & Expo
  • Place of Presentation: San Francisco
  • Year and Date: 2013-06-17
• [Presentation] 子宮内膜症に特異的なゲノムDNAメチル化修飾の検証 (2012)
  • Author(s): 伊澤正郎、谷口文紀、原田省
  • Organizer: 第17回日本生殖内分泌学会学術総会
  • Place of Presentation: 東京都
  • Year and Date: 2012-12-08
• [Presentation] 子宮内膜症におけるエストロゲン受容応答システムの分子基盤解析 (2012)
  • Author(s): 伊澤正郎
  • Organizer: 日本レチノイド研究会第23回学術集会
  • Place of Presentation: 米子市
  • Year and Date: 2012-11-20
• [Presentation] Genome-wide profiling of DNA methylation in endometriotic cells (2012)
  • Author(s): Izawa M, Taniguchi F and Harada T
  • Organizer: The 2nd Asian Conference on Endometriosis
  • Place of Presentation: Istanbul
  • Year and Date: 2012-11-10
• [Presentation] Re-Evaluation of estrogen receptor expression in endometriotic cells (2012)
  • Author(s): Izawa M, Taniguchi F, Kiyama T, Terakawa N and Harada T
  • Organizer: The 94th Annual Meeting of Endocrine Society
  • Place of Presentation: Houston
  • Year and Date: 2012-06-23
• [Presentation] 子宮内膜症におけるエストロゲン受容体システムの分子基盤解析 (2012)
  • Author(s): 伊澤正郎、原田省
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2012-04-19
• [Presentation] 子宮内膜症とエストロゲン受容体システム (2012)
  • Author(s): 伊澤正郎
  • Organizer: 鳥取県北東アジア学術交流事業セミナー
  • Place of Presentation: 鳥取大学医学部(米子)(招待講演)
  • Year and Date: 2012-02-23
• [Presentation] 子宮内膜症細胞におけるアロマターゼ遺伝子発現とエピジェネティック制御 (2012)
  • Author(s): 伊澤正郎
  • Organizer: 第33回日本エンドメトリオーシス学会
  • Place of Presentation: ホテル長崎(長崎)(招待講演)
  • Year and Date: 2012-01-21
• [Presentation] 子宮内膜症細胞におけるエストロゲン受容体遺伝子メチル化修飾の検証 (2011)
  • Author(s): 伊澤正郎
  • Organizer: 第16回日本生殖内分泌学会学術集会
  • Place of Presentation: シェーンバッハ・サボー(東京)
  • Year and Date: 2011-11-18
• [Presentation] A hypomethylated CpG island in the aromatase gene may cause up-regulation in endometriotic cells (2011)
  • Author(s): Izawa M, Taniguchi F, Terakawa N and Harada T
  • Organizer: The 11th World Congress on Endometriosis
  • Place of Presentation: Montpellier
  • Year and Date: 2011-09-06
• [Presentation] Molecular basis of estrogen receptor alpha expression in endometnotic cells. (2011)
  • Author(s): Izawa M
  • Organizer: The 11th World Congress on Endometriosis
  • Place of Presentation: Corum Montpellier (Montpellier, France)
  • Year and Date: 2011-09-04
• [Presentation] A hypomethylated CpG island in the aromatase gene may cause up-regulation in endometriotic cells (2011)
  • Author(s): Izawa M, Taniguchi F, Iwabe T, Terakawa N and Harada T
  • Organizer: The 93rd Annual Meeting of Endocrine Society
  • Place of Presentation: Boston
  • Year and Date: 2011-06-06
• [Presentation] A hypomethylated CpG island in aromatase gene may cause up-regulation in endometriotic cells. (2011)
  • Author(s): Izawa M
  • Organizer: The 93rd Annual Meeting of Endocrine Society
  • Place of Presentation: Boston Convention Center (Boston, MA, USA)
  • Year and Date: 2011-06-06
• [Presentation] Aberrant expression of IAP family in endometriotic cells may cause resistance to apoptosis. (2011)
  • Author(s): Izawa M (Taniguchi F)
  • Organizer: The 93rd Annual Meeting of Endocrine Society
  • Place of Presentation: Boston Convention Center (Boston, MA, USA)
  • Year and Date: 2011-06-06
• [Presentation] 子宮内膜症におけるエストロゲン受容体α型発現の分子基盤 (2010)
  • Author(s): 伊澤正郎
  • Organizer: 第15回日本生殖内分泌学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪)
  • Year and Date: 2010-11-21
• [Presentation] Epigenetic disorder and up-regulation of aromatase gene in endometriotic cells (2010)
  • Author(s): Izawa M, Taniguchi F and Harada T
  • Organizer: The 1st Asian Conference on Endometriosis
  • Place of Presentation: Shanghai
  • Year and Date: 2010-10-16
• [Presentation] An epigenetic disorder associated with aberrant demethylation of a promoter-distal CpG island in aromatase gene may cause the up-regulation in endometriotic tissues (2010)
  • Author(s): Izawa M
  • Organizer: The first Asian Conference on Endometriosis
  • Place of Presentation: Shanghai Plaza Royale Hotel(上海、中国)(招待講演)
  • Year and Date: 2010-10-16
• [Presentation] The mechanism of resistance to apoptosis in endometriosis (2010)
  • Author(s): Izawa M
  • Organizer: The first Asian Conference on Endometriosis
  • Place of Presentation: Shanghai Plaza Royale Hotel(上海、中国)(招待講演)
  • Year and Date: 2010-10-16
• [Presentation] Further studies on the mode of estrogen receptorα expression in endometriotic cells (2010)
  • Author(s): Izawa M
  • Organizer: The 92^<nd> Annual Meetin of Endocrine Society
  • Place of Presentation: San Diego Convension Center (San Diego, USA)
  • Year and Date: 2010-06-21
• [Presentation] 子宮内膜症間質細胞におけるアロマターゼ遺伝子のエピゲノム障害:非プロモーター領域CpGの異常な脱メチル化 (2010)
  • Author(s): 伊澤正郞、原田省、谷口文紀、岩部富夫、寺川直樹
  • Organizer: 第4回日本エピジェネテュクス研究会
  • Place of Presentation: 米子市
  • Year and Date: 2010-05-27
• [Presentation] 子宮内膜症におけるエストロゲン受容体システムの分子基盤解析
  • Author(s): 伊澤 正郎、谷口 文紀、 寺川 直樹、原田 省
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Re-evaluation of estrogen receptor expression in endometriotic cells
  • Author(s): Izawa M, Taniguchi F, Kiyama T, Terakawa N, Harada T.
  • Organizer: The 94th Annual Meetin of Endocrine Society
  • Place of Presentation: Houston Convention
• [Presentation] 子宮内膜症におけるエストロゲン受容応答システムの分子基盤解析
  • Author(s): 伊澤 正郎
  • Organizer: 日本レチノイド研究会第23回学術集会
  • Place of Presentation: 米子コンベンションセンター
  • Invited
• [Presentation] Genome-wide profiling of DNA methylation in endometriotic cells
  • Author(s): Izawa M, Taniguchi F, Harada T.
  • Organizer: The 2nd Asian Conference on Endometriosis
  • Place of Presentation: Harbiye Military Museum and Culture Center (Istanbul, Turky)
  • Invited
• [Presentation] 子宮内膜症に特異的なゲノムDNAメチル化修飾の検証
  • Author(s): 伊澤 正郎、谷口 文紀、原田 省
  • Organizer: 第17回日本生殖内分泌学会学術総会
  • Place of Presentation: 東京ステーションコンファレンス
• [Presentation] 子宮内膜症におけるアロマターゼ発現とエピゲノム異常
  • Author(s): 伊澤 正郎、谷口 文紀、原田 省
  • Organizer: 第86回日本生化学会 シンポジウム
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] DNA methylation profiles associated with aberrant gene expressions in endometriosis
  • Author(s): Izawa M, Taniguchi F, Terakawa N, Harada T.
  • Organizer: The 95th Annual Meetin of Endocrine Society
  • Place of Presentation: Moscone Center (San Francisco, CA, USA)
• [Presentation] Parthenoide reduces cell proliferation and PGE2 synthesis in human endometriotic stromal cells and inhibits development of endometriosis in murine model
  • Author(s): Taniguchi F, Takai E, Izawa M, Terakawa N, Harada T.
  • Organizer: The 95th Annual Meetin of Endocrine Society
  • Place of Presentation: Moscone Center (San Francisco, CA, USA)
• [Book] Epigenetics in endometriosis (in endometriosis-pathogenesis and treatment) (2014)
  • Author(s): Izawa M, Taniguchi F and Harada T
  • Publisher: Springer(印刷中)
• [Book] Epigenetics in Endometriosis in Endometriosis-Pathogenesis and treatment(分担) (2014)
  • Author(s): Izawa M, Taniguchi F, Harada T.
  • Publisher: Springer