Establishment of the new strategy with REIC/Dkk-3 against androgen independent prostate cancer.

• Project/Area Number: 15K07754
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Ochiai Kazuhiko 日本獣医生命科学大学, 獣医学部, 准教授 (30550488)
• Co-Investigator(Kenkyū-buntansha): 呰上 大吾 日本獣医生命科学大学, 獣医学部, 准教授 (80453934)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 前立腺がん / REIC/Dkk-3 / SGTA / イヌ / ホルモン療法抵抗性 / ARシグナル伝達

Outline of Final Research Achievements

The pathological condition of canine prostate cancer resembles that of human androgen-independent prostate cancer. Both canine and human androgen receptor (AR) signalling are inhibited by overexpression of the dimerized co-chaperone SGTA, which is considered to cause the development of androgen-independency. REIC interferes with SGTA dimerization and rescues AR signalling. This study aimed to assess the effects of REIC and SGTA interactions on AR signalling in the canine androgen-independent prostate cancer cell line CHP-1.
MTH and Halo-tag PD assays showed that canine REIC interacted with SGTA and interfered with SGTA dimerization. Additionally, reporter assays revealed that canine REIC restored AR signalling. Therefore, we confirmed the interaction between canine SGTA and REIC, as well as their role in AR signalling. Our results suggest that this interaction might contribute to the development of a novel strategy for androgen-independent prostate cancer treatment.

Research Products

• [Journal Article] Functional alteration of canine isocitrate dehydrogenase 2 (IDH2) via an R174K mutation (2018)
  • Author(s): Kawakami S, Ochiai K, Kato Y, Michishita M, Hirama H, Obara R, Azakami D, Watanabe M, Omi T
  • Journal Title: J. Vet. Med. Sci. Volume: 80 Issue: 1 Pages: 85-91
  • DOI: 10.1292/jvms.17-0362
  • NAID: 130006321212
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] R132 mutations in canine isocitrate dehydrogenase 1 (IDH1) lead to functional changes. (2018)
  • Author(s): Kawakami S, Ochiai K, Azakami D, Kato Y, Michishita M, Morimatsu M, Ishiguro-Oonuma T, Onozawa E, Watanabe M, Omi T.
  • Journal Title: Vet Res Commun Volume: 42(1) Pages: 49-56
  • DOI: 10.1007/s11259-017-9707-8
  • Peer Reviewed
• [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 Vet Res Volume: 13 Pages: 170-170
  • DOI: 10.1186/s12917-017-1094-4
  • Peer Reviewed / Open Access
• [Journal Article] Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk-3) (2017)
  • Author(s): Ochiai K, Oda H, Shono S, Kato Y, Sugihara S, Nakazawa S, Azakami D, Michishita M, Onozawa E, Bonkobara M, Sako T, Shun-Ai L, Ueki H, Watanabe M, Omi T.
  • Journal Title: Vet Comp Oncol Volume: 印刷中 Pages: 1181-1186
  • DOI: 10.1111/vco.12254
  • Peer Reviewed / Acknowledgement Compliant
• [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. (2017)
  • 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: Vet Comp Oncol Volume: 印刷中 Pages: 557-562
  • DOI: 10.1111/vco.12199
  • Peer Reviewed / Open Access
• [Journal Article] Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity. (2016)
  • Author(s): Ochiai K, Morimatsu M, Kato Y, Ishiguro-Oonuma T, Udagawa C, Rungsuriyawiboon O, Azakami D, Michishita M, Ariyoshi Y, Ueki H, Nasu Y, Kumon H, Watanabe M, Omi T.
  • Journal Title: Oncotarget Volume: 7 Pages: 3283-3296
  • DOI: 10.18632/oncotarget.6488
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer (2015)
  • Author(s): Kato, Y., Ochiai, K., Michishita, M., Azakami, D., Nakahira, R., Morimatsu, M., Ishiguro-Oonuma, T., Yoshikawa, Y., Kobayashi, M., Bonkobara, M., Kobayashi, M., Takahashi, K., Watanabe, M., and Omi, T.
  • Journal Title: The Veterinary Journal Volume: 206 Pages: 143-148
  • DOI: 10.1016/j.tvjl.2015.08.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] イヌIDH1ホモログのクローニングと機能解析 (2017)
  • Author(s): 川上翔太、落合和彦、道下正貴、近江俊徳
  • Organizer: 日本獣医臨床病理学会2017年大会
• [Presentation] がん抑制遺伝子REIC/Dkk-3ネコホモログの構造と乳腺腫瘍に対するアポトーシス誘導能の解析 (2017)
  • Author(s): 落合和彦、杉原思穂、小田民美、川上翔太、平間日奈子、呰上大吾、近江俊徳
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] IDH1イヌホモログの変異が機能におよぼす影響の検討 (2017)
  • Author(s): 川上翔太，落合和彦、尾原涼、道下正貴、近江俊徳
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] CMAH遺伝子解析による猫 AB式血液型の分子基盤 (2017)
  • Author(s): 近江俊徳、中澤翔太、宇田川智野、多田尚美、三井寛子、落合和彦、 加藤由比子、呰上大吾、左向敏紀、筒井敏彦、盆子原誠、土田修一
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] イヌ乳腺腫瘍細胞株で生じたp53遺伝子変異の検出と機能解析 (2017)
  • Author(s): 平間日奈子、落合和彦、道下正貴、近江俊徳
  • Organizer: 第48回日本比較臨床医学会学術集会
• [Presentation] SGTA機能制御を起点とした 前立腺がん新規治療戦略の創出 (2016)
  • Author(s): 加藤由比子，落合和彦，近江俊徳
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] イヌ前立腺がん関連遺伝子SGTAがARシグナル伝達に与える影響の検討 (2016)
  • Author(s): 加藤由比子，落合和彦，近江俊徳
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学生物資源学部（藤沢）
  • Year and Date: 2016-09-06
• [Presentation] 前立腺がん関連遺伝子SGTAイヌホモログの構造および機能解析 (2015)
  • Author(s): 加藤由比子。落合和彦。中平嶺、道下正貴、呰上大吾、高橋公正、近江俊徳
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森）
  • Year and Date: 2015-09-07
• [Presentation] イヌSGTAホモログのクローニングと前立腺がん細胞のアンドロゲンシグナル伝達機構に与える影響の検討 (2015)
  • Author(s): 落合和彦、加藤由比子、中平嶺、道下正貴、呰上大吾、高橋公正、近江俊徳
  • Organizer: 日本獣医臨床病理学会2015年大会
  • Place of Presentation: 日本獣医生命科学大学（東京）
  • Year and Date: 2015-05-30
• [Remarks] 日本獣医生命科学大学獣医学部獣医保健看護学科TOP>>比較遺伝学研究分野
  • URL: http://www.nvlu.ac.jp/veterinary-nursing/members/002.html/