Analysis and detection of the molecules involving hormone refractory prostate cancer by applying Proteomics methodology

• Project/Area Number: 14370517
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: KUBOTA Yoshinobu Yokohama City Univ., Dept. Urology, Professor, 大学院・医学研究科, 教授 (10106312)
• Co-Investigator(Kenkyū-buntansha): UEMURA Hiroji Yokohama City Univ., Dept. Urology, Associate professor, 附属病院, 助教授 (50244439) ; YAO Masahiro Yokohama City Univ., Dept. Urology, Associate professor, 大学院・医学研究科, 助教授 (00260787) ; HIRANO Hisashi Yokohama City Univ., Kihara institute for biological research, Professor, 木原生物学研究所, 教授 (00275075)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥14,300,000 (Direct Cost: ¥14,300,000); Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
• Keywords: prostate cancer / hormone refractory cancer / proteomics / angiotensin II receptor / androgen / アンドロゲン受容体 / 前立線癌

Research Abstract

To analyze the key molecules involving progression of prostate cancer to hormone refractory cancer, we have applied proteomics and other molecular biological methodologies in this research project.
We have identified several molecules which expressed diffentially between androgen dependent prostate cancer cells and androgen independent ones in 2D gel analysis by applying anti-body to tyrosin-kinase. We, then, have focused on the Angiotensin II receptor (AT1) molecules among them.
We demonstrated that AT1 receptar is expressed in human prostate cells. Especially, high expression level of AT1 receptor is seen in androgen independent prostate cancer cells. And stimulation by AII induces activation of intracellular signal transduction pathways that lead to the growth of prostate cancer cells. And we showed that candesartan, an angiatensin II receptor (AT1) blocker, inhibits both the growth of prostate cancer calls in vitro and that of tumors produced by prostate cancer cells in nude mice in vivo (Mol cancer Therap. 2003). We also suggested the potential of AT1 receptor blocker as a novel therapy for prostate cancer (J. Urol. 2005).
We think that these study results have made a remarkable contribution to elucidate the mechanisms of hormone refractory prostate cancer as well as to develop a new novel therapy for this disease.

Research Products

• [Journal Article] Angiotensin II blocker decreases serum prostate specific antigen in hormone refractory prostate cancer. (2005)
  • Author(s): Yamagishi T. et al.
  • Journal Title: The Journal of Urology 173 Pages: 441-441
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity. (2005)
  • Author(s): Ouchi H. et al.
  • Journal Title: International journal of Urology 12 Pages: 73-80
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 前立腺癌における新しい分子標的治療 (2005)
  • Author(s): 上村 博司 他
  • Journal Title: 日本臨床 63・2 Pages: 339-344
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Angiotensin II blocker decreases serum prostate specific antigen in hormone refractory prostate cancer (2005)
  • Author(s): Yamagishi, T., Uemura, H., Nakaigawa, N., Noguchi, K., Kubota, Y.
  • Journal Title: The Journal of Urology 173 Pages: 441-441
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity (2005)
  • Author(s): Ouchi, H., Ishiguro, H., Ikeda, N., Honi, M., Kubota, Y., Uemura, H.
  • Journal Title: International Journal of Urology 12 Pages: 73-80
  • NAID: 10014374307
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity. (2005)
  • Author(s): Ouchi H. et al.
  • Journal Title: International Journal of Urology 12 Pages: 73-80
• [Journal Article] Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy. (2004)
  • Author(s): Uemura H. et al.
  • Journal Title: International Journal of Urology 11・7 Pages: 494-500
  • NAID: 10013441134
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy (2004)
  • Author(s): Uemura, H., Nakamura, M., Hasumi, H., Sugiura, S., Fujinami, K., Miyoshi, Y., Yao, M., Kubota, Y.
  • Journal Title: International Journal of Urology 11(7) Pages: 494-500
  • NAID: 10013441134
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 再燃前立腺癌に対するアンジオテンシンIIレセプターブロッカーの有用性について (2004)
  • Author(s): 上村 博司 他
  • Journal Title: 泌尿器外科 17・8 Pages: 909-913
• [Journal Article] Combination Treatment with 1α,25-Dihydroxyvitamin D_3 and 9-cis-Retinoic Acid Directly Inhibits Human Telomerase Reverse Transcriptase Transcription in Prostate Cancer Cells. (2003)
  • Author(s): Ikeda N. et al.
  • Journal Title: Mol.Cancer Therap. 2 Pages: 739-746
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor. (2003)
  • Author(s): Ishiguro H. et al.
  • Journal Title: Int.J.Cancer 105(1) Pages: 26-32
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Combination Treatment with 1α, 25-Dihydroxyvitamin U3 and 9-cis-Retinoic Acid Directly Inhibits Human Telomerase Reverse Transcriptase Transcription in Prostate Cancer Cells (2003)
  • Author(s): Ikeda, N., Uemura, H., Ishiguro, H., Hori, M, Hosaka, M., Kyo, S., Miyamoto, H., Takeda, E., Kubota, Y.
  • Journal Title: Mol. Cancer Therap. 2 Pages: 739-746
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 55 kDa nuclear matrix (nmt55) mRNA is expressed in human prostate cancer and is associated with androgen receptor (2003)
  • Author(s): Ishiguro, H., Uemura, H., Fujinami, K., Ikeda, N., Ohta, S., Kubota, Y.
  • Journal Title: Int. J. Cancer 105(1) Pages: 26-32
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer (2003)
  • Author(s): Miyoshi, Y., Ishiguro, H., Uemura, H., Fujinami, K., Miyamoto, H., Miyoshi, Y., Kitamura, H., Kubota, Y.
  • Journal Title: The Prostate 56 Pages: 280-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiotensin II Receptor Blocker Shows Antiproliferative Activity in Prostate Cancer Cells: A Possibility of Tyrosine Kinase Inhibitor of Growth Factor (2003)
  • Author(s): Uemura, H., Ishiguro, H., Nakaigawa, N., Nagashima, Y., Miyoshi, Y., Fujnami, K., Sakaguchi, A., Kubota, Y.
  • Journal Title: Mol. Cancer Therap. 2 Pages: 1139-1147
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of AR Associated Protein 55 (ARA55) and Androgen Receptor in Prostate Cancer (2003)
  • Author(s): Miyoshi Y. et al.
  • Journal Title: The Prostate 56 Pages: 280-286
• [Journal Article] Liprin-α 2gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP (2002)
  • Author(s): Fujinami, K., Uemura, H., Ishiguro, H., Kubota, Y.
  • Journal Title: Int. J. Mol. Med. 10 Pages: 173-170
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association of common missense changes in ELAC2 (HPC2) with prostate cancer in a Japanese case-control series (2002)
  • Author(s): Fujiwara, H., Emi, M., Nagai, H., Nishimura, T., Konishi, N., Kubota, Y., Ichikawa, T., Takahashi, S., Shuin, T., Habuchi, T., Qgawa, C., Inoue, K., Skolnick, H.M., Swensen, J., Camp, J.N., Tavtigian, V.S.
  • Journal Title: J. Hum. Genet. 47
  • NAID: 50000725812
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of Growth of Human Prostate Cancer Xenograft by Transfection of p53 gene: Gene Transfer by Electroporation (2002)
  • Author(s): Mikata, K., Uemura, H., Ohuchi, H., Ohta, S., Nagashima, Y., Kubota, Y.
  • Journal Title: Mol. Cancer Therap. 1 Pages: 247-252
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hiroji Uemura et al.: "Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells : A possibility of tyrosine kinase inhibitor of growth factor"Molecular Cancer Therapeutics. 2. 1139-1147 (2003)
• [Publications] Naoya Ikeda, et al.: "Combination Treatment with 1α, 25-Dihydroxyvitamin D3 and 9-cis-Retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells"Molecular Cancer Therapeutics. 2. 739-746 (2003)
• [Publications] Yasuhide Miyoshi, et al.: "Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer"The Prostate. 56. 280-286 (2003)
• [Publications] Hitoshi Ishiguro, et al.: "55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor"Int.J.Cancer. 105. 26-32 (2003)
• [Publications] 窪田 吉信, 三好 康秀: "前立腺がんのジェネティクス"最新医学. 58. 238-251 (2003)
• [Publications] 上村 博司, 窪田 吉信: "再燃前立腺癌に対する治療および緩和治療法について"ホルモンと臨床. 51(6). 67-74 (2003)
• [Publications] 窪田 吉信 編: "前立腺の病気がわかる本"株式会社 法研. 223 (2003)
• [Publications] Mikata K. et al.: "Inhibition of growth of human prostate cancer xenograft by transfection of p53 gene : Gene transfer by electroporation"Molecular Cancer Therapeutics. 1. 247-252 (2002)
• [Publications] Fujinami K. et al.: "Liprin-α2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"Int. J. Mol. Medicine. 10. 173-176 (2002)