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Identification of a novel tumor marker(s), based on the comprehensive analysis of genes expressed selectively in micometastais site.

Research Project

Project/Area Number 16390163
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionKanazawa University

Principal Investigator

MUKAIDA Naofumi  Cancer Research Institute, Professor, がん研究所, 教授 (30182067)

Co-Investigator(Kenkyū-buntansha) 藤井 千文  金沢大学, がん研究所, 助手 (10361982)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsPim-3 / serine / threonine kinase / apoptosis / hepatocellular carcinoma (HCC) / pancreatic cancer / colorectal cancer / liver metastasis / chemokine / CCL2 / CCR1 / CCL3 / 肺転移 / 腫瘍壊死因子 / 血管内皮増殖因子 / スレオニンキナーゼ
Research Abstract

1)Aberrant expression of a proto-oncogene with serine/threonine kinase activity; Pim-3, in malignant lesions of endoderm-derived organs. We compared gene expression patterns in pre-malignant and malignant lesions in murine hepatocarinogenesis model, by using fluorescent differential display method. As a result, we observed that a proto-oncogene with serine/threonine kinase activity, Pim-3 was aberrantaly expressed in pre-malignant and malignant lesions, but not normal hepatic tissues. Similar observations were obtained also on human hepatocellular carcinoma (HCC) and normal liver tissues. Pim-3 was constitutively expressed in human HCC cell lines and the inhibition of Pim-3 expression by short interfering RNA induced the apoptosis of human HCC cell lines. Pim-3 was not detected in other endoderm-derived organs such as pancreas and colon, but its expression was enhanced in the pre-malignant lesions and malignant lesions of these organs. In both human pancreatic cancer and colorectal can … More cer cell lines, Pim-3 was constitutively expressed and a pro-apoptotic molecule, Bad was co-localized with Pim and was phosphorylated at 112-Ser, which represents its inactive form. The inhibition of Pim-3 expression by short interfering RNA reduced the phosphorylation of Bad at 112-Ser and the expression of an anti-apoptotic molecule, Bcl-XL and eventually enhanced the apoptosis. These observations suggest that aberrant expression of Pim-3 can contribute to carcinogenesis in endoderm-derived organs, including liver, pancreas, and colon, by inhibiting apoptosis and that Pim-3 can be a novel tumor marker to detect pre-malignant and malignant lesions of these organs.
2)Roles of chemokines and hepatocarcinogenesis and liver metastasis We observed that a chemokine, CCL3 and its receptor, CCR1, can inhibit the carcinogenesis in the early phase of murine hepatocarcinogenesis induced by diethylnitrosamine administration but that the CCL3-CCR1 axis can promote carcinogenesis of the same hepatocarcinogenesis, by inducing angiogenesis. We further demonstrated that another chemokine, CCL2 and its receptor, CCR2, can promote liver metastasis by activating hepatic stellate cells (Ito cells) and eventually accelerating neovascularization. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (30 results)

All 2007 2006 2005 2004 Other

All Journal Article (28 results) Book (2 results)

  • [Journal Article] A proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis.2007

    • Author(s)
      Popivanova BK, Li Y-Y, Zhen H, Omura K, Fujii C, Tsuneyama K, Mukaida N
    • Journal Title

      Cancer Science 98(3)

      Pages: 321-328

    • NAID

      10019481422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis.2007

    • Author(s)
      Popivanova BK, Li Y-Y, Zheng H, Omura K, Fujii C, Tsuneyama K, Mukaida N
    • Journal Title

      Cancer Science 98 (3)

      Pages: 321-328

    • NAID

      10019481422

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis.2007

    • Author(s)
      Popivanova BK, Li Y-Y, Zheng H, Omura K, Fujii C, Tsuneyama K, Mukaida N
    • Journal Title

      Cancer Science 98(3)

      Pages: 321-328

    • NAID

      10019481422

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intrahepatic interleukin-8 production during disease progression of chronic hepatitis C.2007

    • Author(s)
      Tachibana Y, Nakamoto Y, Mukaida N, Kaneko S.
    • Journal Title

      Cancer Letter 251(1)

      Pages: 36-42

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages, and neovascularization.2006

    • Author(s)
      Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C, Mukaida N
    • Journal Title

      International Journal of Cancer 118 (2)

      Pages: 335-345

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression.2006

    • Author(s)
      Yang X, Lu P, Fujii C, Nakamoto Y, Gao J-L, Kaneko S, Murphy PM, Mukaida N
    • Journal Title

      International Journal of Cancer 118 (8)

      Pages: 1869-1876

    • NAID

      120000809415

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates Bad to block Bad-mediated apoptosis in human pancreatic cancer cell lines.2006

    • Author(s)
      Li Y-Y, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N
    • Journal Title

      Cancer Research 66 (13)

      Pages: 6741-6747

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages, and neovascularization.2006

    • Author(s)
      Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C, Mukaida, N.
    • Journal Title

      International Journal of Cancer 118 (2)

      Pages: 335-345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression.2006

    • Author(s)
      Yang X, Lu P, Fujii C, Nakamoto Y, Gao J-L, Kaneko S, Murphy PM, Mukaida N.
    • Journal Title

      International Journal of Cancer 118 (8)

      Pages: 1869-1876

    • NAID

      120000809415

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates Bad to block Bad-mediated apoptosis in human pancreatic cancer cell lines.2006

    • Author(s)
      Li Y-Y, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N.
    • Journal Title

      Cancer Research 66 (13)

      Pages: 6741-6747

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Attenuated liver fumor formation in the absence of CCR2 with a concomitant reduction reduction in the accumulation of hepatic stellate cells, macrophages, and neovasculatization.2006

    • Author(s)
      Yang X., Lu P, Ishida Y, Kuziel Wa, Fujii C, Mukaida, N.
    • Journal Title

      International Journal of Cancer 118(2)

      Pages: 335-345

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Essential contribution of a chemokine, CCL3、and its receptor CCR1,to hepatocellular carcinoma progression.2006

    • Author(s)
      Yang X, Lu P, Fujii C, Nakamoto Y, Gao J-L, Kaneko S, Murphy PM, Mukaida N.
    • Journal Title

      International Journal of Cancer 118(8)

      Pages: 1869-1876

    • NAID

      120000809415

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pim-3,a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates Bad to block Bad-mediated apoptosis in human pancreatec cancer cell lines.2006

    • Author(s)
      Li Y-Y, Popivanova BK, Nagai Y, Ishikura H, Fujii C, Mukaida N.
    • Journal Title

      Cancer Research 66(13)

      Pages: 6741-6747

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages, and neovascularization.2006

    • Author(s)
      Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C, Mukaida, N.
    • Journal Title

      International Journal of Cancer 118(2)

      Pages: 335-345

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression.2006

    • Author(s)
      Yang X, Lu P, Fujii C, Nakamoto Y, Gao J-L, Kaneko S, Murphy PM, Mukaida N.
    • Journal Title

      International Journal of Cancer 118(8)

      Pages: 1869-1876

    • NAID

      120000809415

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines.2005

    • Author(s)
      Fujii C, Nakamoto Y, Lu P, Tsuneyama K, Popivanova B, Kaneko S, Mukaida N
    • Journal Title

      International Journal of Cancer 114

      Pages: 209-218

    • NAID

      120000809434

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines.2005

    • Author(s)
      Fujii C, Nakamoto Y, Lu P, Tsuneyama K, Popivanova B, Kaneko S, Mukaida N.
    • Journal Title

      International Journal of Cancer 114

      Pages: 209-218

    • NAID

      120000809434

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.2005

    • Author(s)
      Kuroda T, Kitadai Y, Tanaka S, Yang X, Mukaida N, Yoshihara M, Chayama K
    • Journal Title

      Clinical Cancer Research 11(21)

      Pages: 7629-7636

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines2005

    • Author(s)
      Fujii C, Nakamoto Y, Lu P, Tsuneyama K, Popivanova B, Kaneko S, Mukaida N
    • Journal Title

      International Journal of Cancer (in press)

    • NAID

      120000809434

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55.2004

    • Author(s)
      Tomita Y, Yang X, Ishida Y, Nemoto-Sasaki Y, Kondo T, Oda M, Watanabe G, Chladakov GN, Fujii C, Mukaida N
    • Journal Title

      International Journal of Cancer 112(6)

      Pages: 927-933

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55.2004

    • Author(s)
      Tomita Y, Yang X, Ishida Y, Nemoto-Sasaki Y, Kondo T, Oda M, Watanabe G, Chladakov GN, Fujii C, Mukaida N.
    • Journal Title

      International Journal of Cancer 112 (6)

      Pages: 927-933

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cancer gene therapy using cytokine and chemokine genes.2004

    • Author(s)
      Mukaida N.
    • Journal Title

      Annals of Cancer Research and Therapy 12

      Pages: 33-51

    • NAID

      130000120347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55.2004

    • Author(s)
      Tomita Y, Yang X, Ishida Y, Fujii C, Mukaida N. et al.
    • Journal Title

      International Journal of Cancer 112(6)

      Pages: 927-933

    • Related Report
      2004 Annual Research Report
  • [Journal Article] hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin2004

    • Author(s)
      Nakamura M, Kyo S, Kanaya T, Yatabe N, Fujii C, Mukaida N, et al.
    • Journal Title

      Cancer Gene Therapy 11(1)

      Pages: 1-7

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells2004

    • Author(s)
      Hwang YS, Jeong M, Park JS, Kim L, Lee DB, Shin BA, Mukaida N, et al.
    • Journal Title

      Oncogene 23

      Pages: 6603-6611

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The essential involvement of cross-talk between IFN-γ and TGF-β in the skin wound-healing process2004

    • Author(s)
      Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N
    • Journal Title

      Journal of Immunology 172(3)

      Pages: 1848-1855

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Essential involvement of IFN-γ in Clostridium difficile toxin A-induced enteritis2004

    • Author(s)
      Ishida Y, Maegawa T, Kondo T, Kimura A, Iwakura Y, Nakamura S, Mukaida N
    • Journal Title

      Journal of Immunology 172(5)

      Pages: 3018-3025

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.

    • Author(s)
      Kagaya T, Nakamoto Y, Sakai Y, Tsuchiyama T, Yagita H, Mukaida N, Kaneko S
    • Journal Title

      Cancer Gene Therapy (In press)

    • Related Report
      2005 Annual Research Report
  • [Book] Chemokines In The Encyclopedia of Endocrine Diseases2004

    • Author(s)
      Mukaida, N
    • Total Pages
      5
    • Publisher
      Elsevier Science Ltd., London
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Chemokines(The Encyclopedia of Endocrine Diseases)2004

    • Author(s)
      Mukaida N
    • Total Pages
      5
    • Publisher
      Elsevier Science Ltd., London
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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