Establishment of a new xenograft model for uterine leiomyoma using sub-renal grafting technique in immunodeficient mice.

2010 Fiscal Year Final Research Report

• Project/Area Number: 21890038
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Chiba University
• Principal Investigator: ISHIKAWA Hiroshi Chiba University, 大学院・医学研究院, 助教 (70553973)
• Project Period (FY): 2009 – 2010
• Keywords: 子宮筋腫 / 免疫不全マウス / 移植モデル / エストロゲン / プロゲステロン / xenograft

Research Abstract

We established a new xenograft model for uterine leiomyoma in which leiomyoma cell pellets were grafted beneath the kidney capsule of super immunodeficient mice. The xenografts enlarged under coadministration of estrogen and progesterone in ovariectomized mice. Then we evaluated the efficacy of RU486, which is a progesterone antagonist, for the reduction of leiomyoma xenograft size in this model. We found that RU486 significantly inhibited the growth of the xenograft even in the presence of both estrogen and progesterone. Finally, we proved that severe immunodeficient mice are suitable as hosts instead of super immunodeficient mice. Our model would be useful for the screening of potential therapeutic agents for the uterine leiomyoma.

Research Products

• [Journal Article] Insulin-Like Growth Factor I Enhances the Expression of Aromatase P450 by Inhibiting Autophagy. (2010)
  • Author(s): Zhang B, Shozu M, Okada M, Ishikawa H, Kasai T, Murakami K, Nomura K, Harada N, Inoue M.
  • Journal Title: Endocrinology. 151(10) Pages: 4949-4958
  • Peer Reviewed
• [Journal Article] LAT1 egulates Growth of Uterine Leiomyoma Smooth Muscle Cells. (2010)
  • Author(s): Luo X, Coon JS 5th, Su E, Pearson EK, Yin P, Ishikawa H, Bulun SE.
  • Journal Title: Reprod Sci. 17(9) Pages: 791-797
  • Peer Reviewed
• [Journal Article] Progesterone is essential for maintenance and growth of uterine leiomyoma. (2010)
  • Author(s): Ishikawa H, Ishi K, Serna VA, Kakazu T, Bulun SE, Kurita T.
  • Journal Title: Endocrinology. 151(6) Pages: 2433-2442
  • Peer Reviewed
• [Journal Article] Transcription Factor KLF11 Integrates Progesterone Receptor Signaling and Proliferation in Uterine Leiomyoma Cells. (2010)
  • Author(s): Yin P, Lin Z, Reierstad S, Wu J, Ishikawa H, Marsh EE, Innes J, Cheng Y, Pearson K, Coon V JS, Kim JJ, Chakravarti D, Bulun SE.
  • Journal Title: Cancer Res. 70(4) Pages: 1722-1730
  • Peer Reviewed
• [Journal Article] 17beta-Hydroxysteroid Dehydrogenase-2 Deficiency and Progesterone Resistance in Endometriosis. (2010)
  • Author(s): Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, Thung S, Xue Q, Marsh EE, Tokunaga H, Ishikawa H, Kurita T, Su EJ.
  • Journal Title: Smin Reprod Med. 28(1) Pages: 44-50
  • Peer Reviewed
• [Journal Article] Progesterone and Mifepristone Regulate L-Type Amino Acid Transporter 2 and 4F2 Heavy Chain Expression in Uterine Leiomyoma Cells. (2009)
  • Author(s): Luo X, Yin P, Reierstad S, Ishikawa H, Lin Z, Pavone ME, Zhao H, Marsh EE, Bulun SE.
  • Journal Title: J Clin Endocrinol Metab. 94(11) Pages: 4533-4539
  • Peer Reviewed
• [Journal Article] High Aromatase Expression in Uterine Leiomyoma Tissues of African-American Women. (2009)
  • Author(s): Ishikawa H, Reierstad S, Demura M, Rademaker AW, Kasai T, Inoue M, Usui H, Shozu M, Bulun SE.
  • Journal Title: J Clin Endocrinol Metab. 94(5) Pages: 1752-1756
  • Peer Reviewed
• [Presentation] マウス腎被膜下移植法を用いた、ヒト子宮筋腫動物実験モデルの作製 (2010)
  • Author(s): 王桂文、石川博士、大見健二、生水真紀夫
  • Organizer: 平成22年度千葉医学会例会産婦人科部会
  • Place of Presentation: 千葉
  • Year and Date: 2010-12-11
• [Presentation] Evaluation of NOD/SCID and nude mice as the host for human uterine leiomyoma xenografts. (2010)
  • Author(s): Ishikawa H, Wang GW, Sone K, Kurita T, Shozu M
  • Organizer: Advances in Uterine Leiomyoma Research : 3rd NIH International Congress.
  • Place of Presentation: Bethesda, MD, USA.
  • Year and Date: 2010-11-23
• [Presentation] Novel in vivo disease model for human uterine leiomyoma : a powerful tool for discovering new therapies. (2010)
  • Author(s): Ishikawa H, Ishi K, Shozu M, Bulun SE, Kurita T
  • Organizer: 20th World Congress on Fertility and Sterility.
  • Place of Presentation: Munich, Germany.
  • Year and Date: 2010-09-15
• [Presentation] 子宮筋腫増殖の鍵はエストロゲンではなくプロゲステロンである:マウス腎被膜下移植法を用いた、新しい動物実験モデルによる検討から (2010)
  • Author(s): 石川博士、碓井宏和、川野みどり、木原真紀、生水真紀夫
  • Organizer: 第62回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-23
• [Presentation] Progesterone is a key player for the growth maintenance of uterine leiomyoma. (2010)
  • Author(s): Ishikawa H, Ishi K, Shozu M, Bulun SE, Kurita T
  • Organizer: 14th International Congress of Endocrinology.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-27
• [Presentation] 子宮筋腫はプロゲステロン依存性腫瘍である-新しい動物実験モデルを使った検証から- (2009)
  • Author(s): 石川博士、金谷裕美、川野みどり、木原真紀、生水真紀夫
  • Organizer: 第14回日本生殖内分泌学会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-28
• [Presentation] Estrogen and progesterone are concurrently required for uterine leiomyoma enlargement in a novel in vivo model. (2009)
  • Author(s): Ishikawa H, Ishi K, Kakazu R, Bulun SE, Kurita T
  • Organizer: American Society for Reproductive Medicine, 65th Annual Meeting.
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2009-10-17
• [Presentation] 重症免疫不全マウス腎被膜下移植法を用いた新しい子宮筋腫in vivo実験モデル (2009)
  • Author(s): 石川博士、碓井宏和、木原真紀、川野みどり、金谷裕美、生水真紀夫
  • Organizer: 第140回日本生殖医学会関東地方部会
  • Place of Presentation: 千葉
  • Year and Date: 2009-06-13