USE OF PIN1 AS A MOLECULAR PROBE TO IDENTIRY PROSTATE CANCER-SPECIFIC BIOMARKERS

• Project/Area Number: 18591765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: RYO Akihide Yokohama City University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF MOLECULAR PATHOLOGY AND ONCOLOGY, ASSOCIATE PROFESSOR (20363814)
• Co-Investigator(Kenkyū-buntansha): UEMURA Hiroshi YOKOHAMA CITY UNIVERSITY, MEDICAL CENTER, DEPARTMENT OF RADIATION ONCOLOGY, 准教授 (50244439)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,070,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥570,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: PROSTATE CANCER / PHOSPHORYLATION / ENZYME / PROTEIN / ULOROGY / タンパク質

Research Abstract

The peptidyl prolyl-isomerase Pinl specifically binds phosphorylated serine or threonine residues immediately preceding proline (pSer/Thr-Pro) in a subset of proteins, and promotes the cis/trans isomerization of the peptide bond. Although Pin 1 has been shown to be involved in cell transformation and maintenance of malignant phenotype in prostate cancer cells (PCa), its specific substrates for malignant transformation remain largely determined. In this study, we utilized Pin 1 as a molecular probe to capture cancer-specific phosphorylated proteins. The glutathione-S-transferase (GST) pull-down and subsequent proteomic analyses newly identified 20 Pca-specific Pin 1 binding proteins(PINBP1-20). We further confirmed up-regulation of these genes in prostate cancer cell lines and tissues. Tissue micro-dissection based quantitative RT-PCR analysis of prostate cancer tissues revealed that the expression of PINBP1 tightly paralleled a higher probability and a shorter period of tumor recurrence following the operation. These results indicate that the Pinl -proteomics analysis can provide a useful tool to identify cancer-specific phosphorylated proteins, which could be potential prognostic marker or anti-cancer targets.

Research Products

• [Journal Article] SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag (2008)
  • Author(s): Ryo A, et. al.
  • Journal Title: Proc Natl Acad Sci USA 105(1) Pages: 294-299
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The wheat germ cell-free based screening of protein substrates of calcium/calmod ulin-dependent protein kinase II delta (2008)
  • Author(s): Masaoka T, et. al.
  • Journal Title: FEBS Lett. 582(13) Pages: 1795-1801
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag (2008)
  • Author(s): Ryo, A, Tsurutani, N, Ohba, K, Kimura, R, Komano, J, Nishi, M, Soeda, H, Hattori, S, Perrem, K, Yamamoto, M, Chiba, J, Mimaya, J, Yoshimura, K, Matsushita, S, Honda, M, Yoshimura, A, Sawasaki, T, Aoki, I, Morikawa, Y, Yamamoto, N
  • Journal Title: Proc Natl Acad Sci U S A. 105(1) Pages: 294-299
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The wheat germ cell-free based screening of protein substrates of calcium/calmodulin - dependent protein kinase II delta (2008)
  • Author(s): Masaoka, T, Nishi, M, Ryo, A, Endo, Y, Sawazaki, T
  • Journal Title: FEBS Lett 582(13) Pages: 1795-1801
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag. (2008)
  • Author(s): Ryo A, et. al.
  • Journal Title: Proceedings of the National Academy of Sciences USA 105(1) Pages: 294-249
  • Peer Reviewed
• [Journal Article] A suppressive role of the prolyl isomerase Pin1 in cellular apoptosis mediated by the death-associated protein Daxx (2007)
  • Author(s): Ryo A, et. al.
  • Journal Title: J Biol Chem. 282(50) Pages: 36671-36681
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A suppressive role of the prolyl-isomerase Pinl in cellular apoptosis mediated by the death-associated protein Daxx (2007)
  • Author(s): Ryo, A, Hirai, A, Nishi, M, Liou, YC, Perrem, K, Lin, SC, Hirano, H, Lee, SW, Aoki, I
  • Journal Title: J Biol Chem 282(50) Pages: 36671-36681
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A suppressive role of the prolyl isomerase Pin1 in cellular apoptosis mediated by the death-associated protein Daxx. (2007)
  • Author(s): Ryo A, et. al.
  • Journal Title: Journal of Biological Chemistry 282(50) Pages: 36671-36681
  • Peer Reviewed
• [Journal Article] Peptidyl-Prolyl Isomerase Pin1 Regulates Interferon Regulatory Factor 3 Signaling to Innate Antiviral Response (2006)
  • Author(s): Saitoh T, et. al.
  • Journal Title: Nature Immunol 7(6) Pages: 589-605
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prolyl-isomerase Pin1 accumulates in levy bodies of parkinson disease and facilit ates formation of alpha-synuclein inclusions (2006)
  • Author(s): Ryo A, et. al.
  • Journal Title: J Biol Chem. 281(7) Pages: 4117-4125
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Pin1 is a novel regulator of centrosome duplication (2006)
  • Author(s): Suizu F, et. al.
  • Journal Title: Mol Cell Biol. 26(4) Pages: 1463-1479
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] An immunohistochemical scoring system of prolyl isomerase Pin1 for predicting relapse of prostate carcinoma after radical prostatectomy (2006)
  • Author(s): Sasaki T, et. al.
  • Journal Title: Pathol Res Pract. 202(5) Pages: 357-364
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Peptidyl-Prolyl Isomerase Pinl Regulates Interferon Regulatory Factor 3 Signaling to Innate Antiviral Response (2006)
  • Author(s): Saitoh, T, Tun-Kyi, A, Ryo, A, Yamamoto, M, Finn, G, Fujita, T, Shizuo, A, Yamamoto, N, Lu, KP, Yamaoka, S
  • Journal Title: Nature Immunol 7(6) Pages: 598-605
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prolyl-isomerase Pinl accumulates in lewy bodies of parkinson disease and facilitates formation of alpha-synuclein inclusions (2006)
  • Author(s): Ryo, A, Togo, T, Nakai, T, Hirai, A, Nishi, M, Yamaguchi, A, Suzuki, K, Hirayasu, Y, Kobayashi, H, Perrem, K, Liou, YC, Aoki, I
  • Journal Title: J Biol Chem 281(7) Pages: 4117-4125
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pinl is a novel regulator of centrosome duplication (2006)
  • Author(s): Suizu, F, Ryo, A, Wulf, G, Lim, J, Lu, KP
  • Journal Title: Mol Cell Biol 26(4) Pages: 1463-1479
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An immunohistochemical scoring system of prolyl isomerase Pinl for predicting relapse of prostate carcinoma after radical prostatectomy (2006)
  • Author(s): Sashki, T, Ryo, A, Uemura, H, Ishiguro, H, Inayama, Y, Yamanaka, S, Kubota, Y, Nagashima, Y, Harada, M, Aoki, I
  • Journal Title: Pathol Res Pract 202(5) Pages: 357-364
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Peptidyl-Prolyl Isomerase Pin1 Regulates Interferon Regulatory Factor 3 Signaling to Innate Antiviral Response. (2006)
  • Author(s): Saitoh, T et al.
  • Journal Title: Nature Immunology 7・6 Pages: 598-605
• [Journal Article] The Pin1 score, a novel prognostic marker of prostate cancer after total prostatectomy. (2006)
  • Author(s): Sasaki, T et al.
  • Journal Title: Pathology Research and Practice 202・5 Pages: 357-364
• [Journal Article] Prolyl-isomerase Pin1 is accumulated in Lewy bodies of Parkinson's disease and facilitates the formation of alpha-synuclein inclusions. (2006)
  • Author(s): Ryo, A et al.
  • Journal Title: Journal of Biological Chemistry 281・7 Pages: 4117-4125
• [Journal Article] Pin1 is a novel regulator of centrosome duplication. (2006)
  • Author(s): Suizu, F et al.
  • Journal Title: Molecular and Cellular Biology 26・4 Pages: 1463-1479
• [Presentation] Use of Pinl as a molecular probe to identify novel anti-cancer targets in prostate cancer (2007)
  • Author(s): 梁 明秀
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Post-translational regulation of HIV-1 protein reveals a novel virus-host cell interaction for HIV-1 infection (2007)
  • Author(s): 梁 明秀
  • Organizer: 第21回日本エイズ学会総会
  • Place of Presentation: 広島
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Use of Pinl as a molecular probe to identify novel anti-cancer targets in prostate cancer (2007)
  • Author(s): Ryo, A
  • Organizer: 96th Annual Meeting of Japanese Association of Pathology
  • Place of Presentation: Osaka
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Post-translational regulation of HIV-1 protein reveals a novel virus-host cell interaction for HIV-1 infection (2007)
  • Author(s): Ryo, A
  • Organizer: 21st Annual Meeting of Japanese Society for AIDS Research
  • Place of Presentation: Hiroshima
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Use of Pin1 as a molecular probe to identify cancer-specific phosphorylated proteins (2006)
  • Author(s): Ryo A, et. al.
  • Organizer: Molecular Diagnostics Cancer Research
  • Place of Presentation: Chicago, USA
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Identification and characterization of a novel host factor for HIV-1 infection by serial analysis of gene expression(SAGE)technology (2006)
  • Author(s): Ryo A
  • Organizer: 7th Kumamoto AIDS seminar
  • Place of Presentation: Kumamoto, Japan
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Proryl-isomerase Pin1 facilitates the formation of a-synuclein inclusions (2006)
  • Author(s): 梁明 秀, 他
  • Organizer: 第94回日本病理学会総会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ペプチジルプロリルイソメラーゼPin1の分子病理学 (2006)
  • Author(s): 梁明 秀
  • Organizer: 第52回日本病理学会秋期と特別総会(A演説、学術研究賞)
  • Place of Presentation: 和歌山
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of SOCS-box Proteins in HIV-1 Infection and Traffcking of the HIV-1 Gag (2006)
  • Author(s): Ryo A, et. al.
  • Organizer: 第20回日本エイズ学会シンポジウム
  • Place of Presentation: 東京
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Use of Pinl as a molecular probe to identify cancer-specific phosphorylated proteins (2006)
  • Author(s): Ryo, A, Nishi, M, Aoki, I
  • Organizer: Molecular Diagnostics Cancer Research(AACR Molecular Diagnostics in Cancer Therapeutic Development)
  • Place of Presentation: Chicago, IL
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Identification and characterization of a novel host factor for HIV-1 infection by serial analysis of gene expression (SAGE) technology (2006)
  • Author(s): Ryo, A
  • Organizer: 7th Kumamoto AIDS seminar Kumamoto
  • Place of Presentation: Kumamoto. (invited speaker)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Proryl-isomerase Pinl facilitates the formation of α-synuclein inclusions (2006)
  • Author(s): Ryo, A
  • Organizer: 94th Annual Meeting of Japanese Association of Pathology
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Molecular pathology of prolyl-isomerase Pin 1 (2006)
  • Author(s): Ryo, A
  • Organizer: 52nd Autumn Meeting of Japanese Association of Pathology
  • Place of Presentation: Wakayama. (invited speaker)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Role of SOCS-box Proteins in HIV-1 Infection and Traffcking of the HIV-1 Gag (2006)
  • Author(s): Ryo, A
  • Organizer: 20th Annual Meeting of Japanese Society for AIDS Research
  • Place of Presentation: Tokyo
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] 前立腺癌の検出方法及び前立腺癌の術後再発の可能性の判定方法 (2007)
  • Inventor(s): 梁 明秀、青木 一郎、平野 久、遠藤 寛二
  • Industrial Property Rights Holder: 公立大学法人 横浜市立大学
  • Industrial Property Number: 2007-255081
  • Filing Date: 2007-09-28
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] 前立腺癌の検出方法及び前立腺癌の術後再発の可能性の判定方法 (2007)
  • Inventor(s): 梁 明秀、青木一郎、平野久、遠藤寛二
  • Industrial Property Rights Holder: 公立大学法人横浜市立大学
  • Industrial Property Number: 2007-255081
  • Filing Date: 2007-09-28
• [Patent(Industrial Property Rights)] 前立腺癌の予後判定方法及びそのための診断薬 (2006)
  • Inventor(s): 梁 明秀, 青木一郎, 佐々木毅
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 2006-104315
  • Filing Date: 2006-04-22