Elucidation of the unitary regulation on the malignant transformation and androgen insensitivity in prostate cancer.

• Project/Area Number: 15H04297
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Okayama University
• Principal Investigator: Watanabe Masami 岡山大学, 大学病院, 教授 (70444677)
• Co-Investigator(Kenkyū-buntansha): 黄 鵬 岡山大学, 医歯薬学総合研究科, 助教 (00610841) ; 野口 洋文 琉球大学, 医学(系)研究科(研究院), 教授 (50378733) ; 植木 英雄 岡山大学, 医学部, 技術専門職員 (90537218)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 前立腺癌 / 内分泌療法抵抗性 / REIC/Dkk-3 / 細胞骨格 / 男性ホルモン / SGTA / 悪性形質 / 代謝 / がん制御遺伝子 / 腫瘍学 / 前立腺

Outline of Final Research Achievements

Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3, a tumor suppressor gene, induces apoptosis in cancer cells when overexpressed in the cells. In this study, we disclosed the significance of REIC/DKK-3 in the development of androgen-independent prostate cancer involving the regulation of Ras signaling and androgen sensitivity. Furthermore, we obtained findings that provide novel insights to improve the understanding of cytoskeleton based molecular transport system which could be associated with the molecular functions of REIC/Dkk-3.

Academic Significance and Societal Importance of the Research Achievements

癌治療遺伝子REIC/Dkk-3を用いた前立腺癌に対するin situ遺伝子治療の臨床研究では、癌細胞において細胞死が誘導されることが示されている。本研究の学術的な成果は、特に臨床の現場で問題となる内分泌療法抵抗性前立腺癌の発生制御に関わる細胞内因子として、REIC/Dkk-3タンパク質およびその関連タンパク質群の存在を明らかにしたことにある。これらのタンパク質群の更なる分子的・機能的解析を行うことにより、前立腺癌をはじめとする各種癌疾患に対する新規の医薬品開発につながることが期待される。

Research Products

• [Journal Article] Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line. (2018)
  • Author(s): Ochiai K, Azakami D, Morimatsu M, Hirama H, Kawakami S, Nakagawa T, Michishita M, Egusa AS, Sasaki T, Watanabe M, Omi T.
  • Journal Title: Oncol Rep Volume: 40 Pages: 488-494
  • DOI: 10.3892/or.2018.6409
  • NAID: 120006551592
  • Peer Reviewed / Open Access
• [Journal Article] Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines (2017)
  • Author(s): Kato Yuiko、Ochiai Kazuhiko、Kawakami Shota、Nakao Nobuhiro、Azakami Daigo、Bonkobara Makoto、Michishita Masaki、Morimatsu Masami、Watanabe Masami、Omi Toshinori
  • Journal Title: BMC Veterinary Research Volume: 13 Issue: 1 Pages: 170-170
  • DOI: 10.1186/s12917-017-1094-4
  • Peer Reviewed / Open Access
• [Journal Article] The canine prostate cancer cell line CHP-1 shows over-expression of the co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (2016)
  • Author(s): Azakami, D., Nakahira, R., Kato, Y., Michishita, M., Kobayashi, M., Onozawa, E., Bonkobara, M., Kobayashi, M., Takahashi, K., Watanabe, M., Ishioka, K., Sako, T., Ochiai, K., and Omi, T.
  • Journal Title: Veterinary and Compapative Oncology Volume: 印刷中 Issue: 2 Pages: 557-562
  • DOI: 10.1111/vco.12199
  • Peer Reviewed / Open Access
• [Journal Article] The induction of antigen-specific CTL by in situ Ad-REIC gene therapy. (2016)
  • Author(s): Ariyoshi Y, Watanabe M, Eikawa S, Yamazaki C, Sadahira T, Hirata T, Araki M, Ebara S, Nasu Y, Udono H, Kumon H.
  • Journal Title: Gene Ther. Volume: gt.2016.7 Issue: 5 Pages: 408-414
  • DOI: 10.1038/gt.2016.7
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic anti-pancreatic cancer immunological effects by treatment with REIC/DKK3 protein and peripheral blood mononuclear cells. (2015)
  • Author(s): Uchida D, Shiraha H, Kato H, Sawahara H, Nagahara T, Iwamuro M, Kataoka J, Horiguchi S, Watanabe M, Takaki A, Nouso K, Nasu Y, Kumon H, Yamamoto K
  • Journal Title: J Gastroenterol Hepatol Volume: - Issue: 6 Pages: 1154-1159
  • DOI: 10.1111/jgh.13259
  • Peer Reviewed / Open Access