去勢抵抗性前立腺癌におけるFOXA1の機能解析と予後予測ノモグラムの構築

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25462469
• Research Institution: Chiba University
• Principal Investigator: 坂本 信一 千葉大学, 医学(系)研究科(研究院), 助教 (70422235)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Androgen Receptor / Prostate Cancer / FOXA1 / Testosterone / Transporter / Tumor Volume

Outline of Annual Research Achievements

前立腺癌ホルモン療法患者の生検検体を用いてFOXA1の染色を行い、FOXA1の発現が高い患者において去勢抵抗性獲得までの期間が有意に短いことから、去勢抵抗性獲得までの予測因子として、生検時のFOXA1の発現の有用性を報告した。アンドロゲン感受性細胞株のLNCAP細胞と去勢抵抗性前立腺癌細胞株であるC4-2 細胞を比較し、LAT1という癌特異的アミノ酸トランスポーターが去勢抵抗性となる過程で上昇することを見出した。また、その原因として、エンザルタミドを含めた抗アンドロゲン剤でアンドロゲン受容体（AR）を阻害すると、LAT1が上昇することを報告した（J Urol　2015）。前立腺癌ホルモン療法患者における血清テストステロンと予後の関連を解析し、日本人ホルモン療法患者（Combined Androgen Blockade）の新規去勢域としてテストステロン20ng/dLの臨床的有用性を提案した（J　Urol　2015）。前立腺癌患者におけるActive Surveillance（AS）の基準と術後の病理学的なInsignificant Cancer（IC）の相関が日本人において低いことから、そのAS基準に前立腺体積を含めることで、欧米並みにICの予測率が上昇することを報告した（Int J Urol　2016）。

Research Products

• [Journal Article] Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells. (2016)
  • Author(s): Xu M, Sakamoto S, Matsushima J, Kimura T, Ueda T, Mizokami A, Kanai Y, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 印刷中 Pages: 印刷中
  • DOI: doi: 10.1016/j.juro.2015.11.071.
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Validation of active surveillance criteria for pathologically insignificant prostate cancer in Asian men. (2016)
  • Author(s): Yamada Y, Sakamoto S, Sazuka T, Goto Y, Kawamura K, Imamoto T, Nihei N, Suzuki H, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 23 Pages: 49-54
  • DOI: doi: 10.1111/iju.12952.
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer. (2016)
  • Author(s): Kurozumi A, Goto Y, Matsushita R, Fukumoto I, Kato M, Nishikawa R, Sakamoto S, Enokida H, Nakagawa M, Ichikawa T, Seki N.
  • Journal Title: Cancer Sci. Volume: 107 Pages: 84-94
  • DOI: doi: 10.1111/cas.12842.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nadir Testosterone after Long-Term Followup Predicts Prognosis in Patients with Prostate Cancer Treated with Combined Androgen Blockade. (2015)
  • Author(s): Kamada S, Sakamoto S, Ando K, Muroi A, Fuse M, Kawamura K, Imamoto T, Suzuki H, Nagata M, Nihei N, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 194 Pages: 1264-70
  • DOI: doi: 10.1016/j.juro.2015.03.120. Epub 2015 Apr 7.
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer. (2015)
  • Author(s): Kato M, Goto Y, Matsushita R, Kurozumi A, Fukumoto I, Nishikawa R, Sakamoto S, Enokida H, Nakagawa M, Ichikawa T, Seki N.
  • Journal Title: Int J Oncol Volume: 47 Pages: 710-8
  • DOI: doi: 10.3892/ijo.2015.3043.
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Testosterone as a significant prognostic factor in CRPC (2016)
  • Author(s): Shinichi Sakamoto
  • Organizer: East Asian Urology Oncology Group
  • Place of Presentation: Seoul Korea
  • Year and Date: 2016-03-25 – 2016-03-25
  • Int'l Joint Research / Invited
• [Presentation] ARを介した前立腺癌進展のメカニズム (2015)
  • Author(s): 坂本 信一
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 愛知県 名古屋市
  • Year and Date: 2015-10-10 – 2015-10-10
  • Int'l Joint Research / Invited
• [Presentation] Tumor volume less than 2.5 ml is a significant cut off value of prognosis in high risk prostate cancer patients (2015)
  • Author(s): Shinichi Sakamoto
  • Organizer: American Urology Association (AUA) Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2015-05-17 – 2015-05-19
  • Int'l Joint Research
• [Presentation] Up regulation of aminoacid transporter LAT1 during androgen deprivation therapy contributes to acquisition of castration resistance in prostate cancer cells (2015)
  • Author(s): Shinichi Sakamoto
  • Organizer: American Urology Association (AUA) Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2015-05-17 – 2015-05-19
  • Int'l Joint Research
• [Presentation] Panel discussion: Prostate cancer-paradigm shift in the treatment of castration resistant prostate cancer (2015)
  • Author(s): Shinichi Sakamoto
  • Organizer: Joint Session of the American Urology Association (AUA) and the Japanese Urological Association (JUA) International Affiliate Society Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2015-05-17 – 2015-05-17
  • Int'l Joint Research / Invited
• [Book] 新前立腺癌 最新の基礎研究と診断・治療 (2016)
  • Author(s): 坂本信一 五島悠介 市川智彦
  • Total Pages: 6
  • Publisher: 日本臨床 ７４巻 増刊号３
• [Funded Workshop] American Urology Association (AUA) (2015)
  • Place of Presentation: New orleans, LA, USA
  • Year and Date: 2015-05-15 – 2015-05-19