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2004 Fiscal Year Final Research Report Summary

Investigation of the function of genes expressed in melanoma/melanocyte with RNA interference for understanding of pigment disorders

Research Project

Project/Area Number 15591193
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

MATSUZAKI Yuriko  Keio University, Department of Medicine, Instructor, 医学部, 助手 (40255435)

Co-Investigator(Kenkyū-buntansha) SUMIMOTO Hidetoshi  Keio University, Department of Medicine, Instructor, 医学部, 助手 (00306838)
KAWAKAMI Yutaka  Keio University, Department of Medicine, Professor, 医学部, 教授 (50161287)
Project Period (FY) 2003 – 2004
KeywordsRNA interference / melanocyte-specific gene / melanoma / melanin synthesis
Research Abstract

We attempted to analyze function of melanocyte-specific genes(MART-1 and AIM-1) and highly expressed genes (β-catenin and FABP7) in melanoma by suppression of gene expression using RNA interference. First we constructed a measurement system that could deduce efficiency of RNA interference by the content of melanin in pigmented melanoma cells. Then we tried to downregulate the MART-1 and the AIM-1 expression with each specific siRNA. The expression of MART-1 and AIM-1 was lowered to 50 and 30 %, respectively, of that in control cells. But there were no changes in the phenotype of melanoma cells at least in growth and migration. β-catenin known as an aberrant accumulated protein in melanoma cells was downregulated with β-catenin specific siRNA. β-catenin protein of 624Amel and 888mel with specific siRNA was decreased less than 20% of control cells and cell proliferation(WST-1 assay) of 624Amel and 888mel with specific siRNA was decreased to 70-80% compared to normal cells. FABP7 identified as a highly expressed gene in melanoma cell lines by DNA chips was then used. When the FABP7 expression was downregulated with FABP7 specific siRNA, in vitro cell proliferation and Matrigel migration of melanoma cell lines, WM266mel and 888mel, were decreased. In contrary, cell proliferation and Matrigel migration of 293T cells with plasmid FABP7 was increased. These results suggest that FABP7 may be involved in formation of malignant phenotype of melanoma. We could not detect deference of melanin content or other phenotypes between RNA interfered cells and control cells about MART-1 and AIM-1. In melanoma cells with β-catenin and FABP7 specific siRNA, we could observe suppression of cell proliferation, and we can also detect suppression of cell migration about FABP7. We think RNA interference is a very useful tool for development of functional analysis and molecular target therapy.

  • Research Products

    (13 results)

All 2005 2004 2003

All Journal Article (13 results)

  • [Journal Article] Systematic identification of human melanoma antigens using serial analysis of gene expression (SAGE).2005

    • Author(s)
      Matsuzaki, Y.
    • Journal Title

      Journal of Immunotherapy 28

      Pages: 10-19

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients.2005

    • Author(s)
      Inozume T
    • Journal Title

      International Journal of Cancer 114

      Pages: 283-290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Systematic identification of human melanoma antigens using serial analysis of gene expression(SAGE).2005

    • Author(s)
      Matsuzaki Y, Hashimoto S, Fujita T, Suzuki T, Sakurai T, Matsushima K, Kawakami Y.
    • Journal Title

      J.Immunother. 28

      Pages: 10-19

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients2005

    • Author(s)
      Inozume T, Matsuzaki Y.Kurihara S, Fujita T, Yamamoto A, Aburatani H, Shimada S, Kawakami Y.
    • Journal Title

      Int.J.Cancer 114

      Pages: 283-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunological detection of altered signaling molecules involved in melanoma development.2005

    • Author(s)
      Kawakami Y, Sumimoto H, Fujita T, Matsuzaki Y.
    • Journal Title

      Cancer Metastasis and Reviews 24

      Pages: 377-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of novel bladder cancer antigen, human lipoic acid synthetase, recognized by antibodies in serum of a patient with metastatic bladder cancer2004

    • Author(s)
      Ito, K.
    • Journal Title

      International Journal of Cancer 108

      Pages: 712-724

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of human tumor antigens and its implication for diagnosis and treatment of cancer.2004

    • Author(s)
      Kawakami Y
    • Journal Title

      Cancer Science 95

      Pages: 784-791

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of novel bladder cancer antigen, human lipoic acid synthetase, recognized by antibodies in serum of a patient with metastatic bladder cancer.2004

    • Author(s)
      Ito K, Fujita T, Akada M, Kiniwa Y, Tsukamoto M, Yamamoto A, Matsuzaki Y, Matsushita M, Asano T, Nakamura J, Tachibana M, Hayakawa M, Ikeda H, Murai M, Kawakami Y.
    • Journal Title

      Int J Cancer. 108

      Pages: 712-724

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference2004

    • Author(s)
      Sumimoto H, Miyagishi M, Miyoshi H, Yamagata S, Shimizu A, Taira K, Kawakami Y.
    • Journal Title

      Oncogene. 23

      Pages: 6031-6039

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of human tumor antigens and its implication for diagnosis and treatment of cancer.2004

    • Author(s)
      Kawakami Y, Fujita T, Matsuzaki Y, Sakurai T, Tsukamoto M, Toda M, Sumimoto H.
    • Journal Title

      Cancer Science. 95

      Pages: 784-791

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability2003

    • Author(s)
      Ishikawa, T.
    • Journal Title

      Cancer Research 63

      Pages: 5564-5572

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 臨床遺伝子学'03 -がんのジェネティックス- 皮膚がんのジェネティックス2003

    • Author(s)
      松崎ゆり子, 河上裕
    • Journal Title

      最新医学(最新医学社、大阪) 58

      Pages: 287-294

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tumor-specific Immunological Recognition of Frameshift-mutated Peptidesan Colon Cancer with Microsatellite Instability.2003

    • Author(s)
      Ishikawa T, Fujita T, Suzuki Y, Okabe S, Yuasa Y, Iwai T, Kawakami Y.
    • Journal Title

      Cancer Res. 63(17)

      Pages: 5564-5572

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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