Functional analysis of MID1 that may be a candidate as a therapeutic target for castration-resistant prostate cancer

• Project/Area Number: 24590463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya City University
• Principal Investigator: TAKAHASHI Satoru 名古屋市立大学, 医学(系)研究科(研究院), 教授 (60254281)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Shugo 名古屋市立大学, 大学院医学研究科, 研究員 (60363933) ; SATO Shinya 名古屋市立大学, 大学院医学研究科, 研究員 (30464564)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 前立腺癌 / MID1/TRIM18 / アンドロゲン受容体 / コアクチベーター / alphaB-crystallin / 転写活性 / MID1 / coactivator

Outline of Final Research Achievements

We have established an androgen-independent (AI) subline from androgen-dependent LNCaP cells, and examined genes differentially expressed between LNCaP and LNCaP-AI by microarray analysis. We thereby found midline 1 (MID1) to be an upregulated gene in the latter. Knockdown of MID1 expression in LNCaP-AI cells resulted in significant suppression of invasion, and enforced expression of MID1 in LNCaP promoted an invasive capacity in the Matrigel chemoinvasion assay. MID1 also promoted AR transcriptional activity in gene dosage-dependent manner by luciferase reporter assay. CRYAB, one of upregulated gene in LNCaP-AI cells, promoted invasive ability and knockdown of it led to suppress invasion of prostate cancer cells in the same as MID1. However, interaction between MID1 and CRYAB did not confirmed by immunocytochemistry. These results suggest that MID1 is an AR coactivator and deeply involved in prostate cancer progression via CRYAB with an indirect manner.

Research Products

• [Journal Article] GPX2 overexpression is involved in cell proliferation and prognosis of castration resistant prostate cancer. (2014)
  • Author(s): Naiki, T., Naiki-Ito, A., Asamoto, M., Kawai, N., Tozawa, K., Etani, T., Sato, S., Suzuki, S., Shirai, T., Kohri, K., Takahashi, S.
  • Journal Title: Carcinogenesis Volume: in press Issue: 9 Pages: 1962-1967
  • DOI: 10.1093/carcin/bgu048
  • Peer Reviewed
• [Journal Article] Establishment of an invasive prostate cancer model in transgenic rats by intermittent testosterone administration. (2014)
  • Author(s): Sato, S., Suzuki, S., Naiki-Ito, A., Komiya, M., Long, N., Kato, H., Sagawa, H., Yamashita, Y., Shirai, T., Takahashi, S.
  • Journal Title: J Toxicol Pathol Volume: 27 Pages: 43-49
  • NAID: 130003382476
  • Peer Reviewed
• [Journal Article] Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis (2013)
  • Author(s): Suzuki S, Shiraga K, Sato S, Punfa W, Naiki-Ito A, Yamashita Y, Shirai T, Takahashi S
  • Journal Title: Cancer Sci Volume: 104巻12号 Issue: 12 Pages: 1711-7
  • DOI: 10.1111/cas.12292
  • Peer Reviewed
• [Journal Article] Apocynin, an NADPH oxidase inhibitor, suppresses progression of prostate cancer via Rac1 dephosphorylation. (2013)
  • Author(s): Suzuki, S., Pitchakarn, P., Sato, S., Shirai, T., Takahashi, S.
  • Journal Title: Exp Toxicol Pathol Volume: 65 Issue: 7-8 Pages: 1035-1041
  • DOI: 10.1016/j.etp.2013.03.002
  • Peer Reviewed
• [Journal Article] Ellagic acid inhibits migration and invasion by prostate cancer cell lines. (2013)
  • Author(s): Pitchakarn, P., Chewonarin, T., Ogawa, K., Suzuki, S., Asamoto, M., Takahashi, S., Shirai, T., Limtrakul, P.
  • Journal Title: Asian Pac J Cancer Prev Volume: 14 Issue: 5 Pages: 2859-2863
  • DOI: 10.7314/apjcp.2013.14.5.2859
  • Peer Reviewed
• [Journal Article] Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate Cancer bone metastasis in a novel rat model (2013)
  • Author(s): Kobayashi Daichi, Kawai Noriyasu, Sato S, Naiki T, Yamada Kenji, Yasui T, Tozawa Keiichi, Kobayashi Takeshi, Takahashi S, Kohri Kenjiro
  • Journal Title: The Prostate Volume: 73 Issue: 9 Pages: 913-922
  • DOI: 10.1002/pros.22637
  • Peer Reviewed
• [Journal Article] 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in benign prostate and subsequent risk for prostate cancer. (2013)
  • Author(s): Tang D, Kryvenko ON, Wang Y, Trudeau S, Rundle A, Takahashi S, Shirai T, Rybicki BA.
  • Journal Title: Int J Cancer Volume: in press Issue: 4 Pages: 961-971
  • DOI: 10.1002/ijc.28092
  • Peer Reviewed
• [Journal Article] Purple corn color inhibition of prostate carcinogenesis by targeting cell growth pathways. (2013)
  • Author(s): Long N, Suzuki S, Sato S, Naiki-Ito A, Sakatani K, Shirai T, Takahashi S
  • Journal Title: Cancer Sci Volume: 104 Issue: 3 Pages: 298-303
  • DOI: 10.1111/cas.12078
  • Peer Reviewed
• [Presentation] 前立腺がん (2014)
  • Author(s): 髙橋 智
  • Organizer: 第15回日本毒性病理学会教育セミナー
  • Place of Presentation: 大阪市立大学医学部（大阪市）
  • Year and Date: 2014-11-15
  • Invited