• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2005 Fiscal Year Final Research Report Summary

Study on identification and application of a novel cancer-associated gene PCA-1 in human prostate carcinoma

Research Project

Project/Area Number 16390109
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionNara Medical University School of Medicine

Principal Investigator

KONISHI Noboru  Nara Medical University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (20145832)

Co-Investigator(Kenkyū-buntansha) SHIMADA Keiji  Nara Medical University School of Medicine, Department of Pathology, Lecturer, 医学部, 講師 (90336850)
Project Period (FY) 2004 – 2005
Keywordsprostate carcinoma / PCA-1 / differential display / phosphorylation / signal transduction
Research Abstract

The incidence of prostate cancer has increased recently in Japan. Although there is much information relating to molecular events underlying the etiology of prostate cancer, it is still unclear as to how these genetic alterations occur in the tumorigenesis. For potential gene markers for prostate carcinoma, we have molecularly identified genes showing differential expression between prostate cancers and normal tissues using fluorescent differential display (FDD) analysis. We identified a gene, designated prostate cancer antigen-1 (PCA-1), which shows high mRNA expression in prostate cancer. Database analysis of the deduced amino acid sequence of PCA-1 indicated high similarity to Escherichia coli AlkB, a DNA alkylation damage repair enzyme. By immunohistochemistry, PCA-1 was expressed in a high number of both prostate cancer samples and in the atypical cells within high-grade prostatic intraepithelial neoplasias, but not in benign prostatic hyperplasia or normal adjacent tissues.
Ubiquitylation and degradation of FLICE-like inhibitory protein (FLIP) was found to be increased and FLIP-dependent Raf-1/extracellular stress-regulated kinase (ERK)/cyclin D1 signal was inhibited by siRNA gene silencing of endogenous PCA-1, resulting in suppression of epidermal growth factor (EGF)-induced cell growth in the human prostate cancer cell line, DU145. FLIP-dependent signaling from PCA-1 was also apparent on paclitaxel stimulation, and apoptosis was enhanced by PCA-1 knock down through down-regulation of Raf-1/ERK. In LNCaP cells with poor endogenous PCA-1 and FLIP, overexpression of PCA-1 promoted EGF-induced cell growth, while attenuating paclitaxel-induced apoptosis through enhanced FLIP/Raf-1 signaling. Both effects were canceled by silencing of FLIP with siRNA. Taken together, the results indicate that PCA-1 is an essential upstream element in FLIP-dependent Raf-1 signaling, playing a critical role in survival of prostate cancer cells.

  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (12 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer2006

    • Author(s)
      Shimada, K., Konishi, N.他2名
    • Journal Title

      Histology and Histopathology 21・4

      Pages: 415-422

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Specific positive and negative effects of FLIP on cell survival in human prostate cancer2006

    • Author(s)
      Shimada, K., Konishi, N.他3名
    • Journal Title

      Carcinogenesis (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] FADD phosphorylation is critical for cell cycle regulation in breast cancer cells2006

    • Author(s)
      Matsuyoshi, S., Konishi, N.他3名
    • Journal Title

      Brit.J. Cancer 94・4

      Pages: 532-539

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer2006

    • Author(s)
      Shimada, K., Nakamura, M., Ishida, E., Konishi, N.
    • Journal Title

      Histol.Histopathol. 21(4)

      Pages: 415-422

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific positive and negative effects of FLIP on cell survival in human prostate, cancer2006

    • Author(s)
      Shimada, K., Nakamura, M., Matsuyoshi, S., Ishida, E., Konishi, N.
    • Journal Title

      Carcinogenesis (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] FADD phosphorylation is critical for cell cycle regulation in breast cancer cells2006

    • Author(s)
      Matsuyoshi, S., Shimada, K., Nakamura, M., Ishida, E., Konishi, N.
    • Journal Title

      Brit.J.Cancer 94(4)

      Pages: 532-539

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] High expression of a new marker PCA-1 in human prostate carcinoma2005

    • Author(s)
      Konishi, N., Shimada, K.他6名
    • Journal Title

      Clin. Cancer Res. 11・14

      Pages: 5090-5097

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular pathology of prostate cancer2005

    • Author(s)
      Konishi, N., Shimada, K.他2名
    • Journal Title

      Pathology International 55・9

      Pages: 531-539

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Phosphorylation status of FADD is associated with prostate cancer progression2005

    • Author(s)
      Shimada, K., Konishi, N.他3名
    • Journal Title

      Journal of Pathology 206・4

      Pages: 423-432

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] High expression of a new marker PCA-1 in human prostate carcinoma2005

    • Author(s)
      Konishi, N., Nakamura, M., Ishida, E., Shimada, K., Mitsui, E., Yoshikawa, R., Yamamoto, H., Tsujikawa, K.
    • Journal Title

      Clin.Cancer Res. 11(14)

      Pages: 5090-5097

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular pathology of prostate cancer2005

    • Author(s)
      Konishi, N., Shimada, K., Ishida, E., Nakamura, M.
    • Journal Title

      Pathol.Int. 55(9)

      Pages: 531-539

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phosphorylation status of FADD is associated with prostate cancer progression2005

    • Author(s)
      Shimada, K., Matsuyoshi, S., Nakamura, M., Ishida, E., Konishi, N.
    • Journal Title

      J.Pathol. 206(4)

      Pages: 423-432

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 抗ヒトPCA-1抗体2004

    • Inventor(s)
      辻川 和丈, 小西 登, 山元 弘
    • Industrial Property Number
      特願 2004-047034
    • Filing Date
      2004-03-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 前立腺癌の判定方法2004

    • Inventor(s)
      辻川 和丈, 小西 登, 山元 弘
    • Industrial Property Number
      特願 2004-047036
    • Filing Date
      2004-03-09
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi