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The prospect of molecular targeted therapy for colon cancer applying keratinocyte growth factor receptor (KGFR) gene silencing.

Research Project

Project/Area Number 16591360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionNIPPON MEDICAL SCHOOL

Principal Investigator

WATANABE Masanori  NIPPON MEDICAL SCHOOL, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (70267227)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
KeywordsColon cancer / Keratinocyte Growth Factor / Keratinocyte Growth Factor Receptor / Antisense Oligonucleotide / Short Interfering RNA / Keratinocyte growth factor / Kerationocyte Growth Factor (KGF) / 増殖因子 / short interfering RNA (siRNA) / antisense oligonucleotide
Research Abstract

[Purpose] Twenty-two kinds of fibroblast growth factor (FGF), which contributes the cell growth and the angiogenesis, have been reported to the present. Among FGF group, FGF-7 (Keratinocyte Growth Factor, KGF) and FGF-10 (KGF-2) are mainly synthesized by mesen-chymal cells, and participate in proliferation of the epitherial cells. Their actions are dependent on their binding to a specific cell-surface KGF receptor (KGFR). This study was performed to clarify the growth inhibitory effects of antisense oligonucleotide and short interfering RNA (siRNA) for keratinocyte growth factor family (KGF, KGF-2, KGFR) on colon cancer cells.
[Materials and Methods] The expression and localization of KGF, KGF-2 and KGFR in human colon cancer tissue and colon cancer cell lines were examined using RT-PCR, immunohistochemistry and in situ hybridization. The recombinant KGF and KGF-2 were administrated into colon cancer cells and growth effects were estimated. The antisense oligonucleotide for KGF and KGF-2 mRNA and the siRNA for KGFR were transferred into colon cancer cell lines and the each growth inhibitory effects were elucidated.
[Results and Discussion] KGF and KGF-2 and their mRNAs were localized in fibroblasts and colon cancer cells. KGFR and its mRNA were localized in colon cancer cells. These findings indicate that KGF and KGF-2 may contribute to colon cancer cell growth via autocrine and paracrine mechanisms. But we failed to obtain a satisfactory result from the study of colon cancer cell growth suppression. It is doubtful that KGF affects the growth of colon cancer precipitately. On the other hand, the study of immunochemistry in colon cancer showed that no KGFR was found in poorly differentiated colon cancer, but it was found in many differentiated colon cancer. Therefore, it is suspected that the affect of KGF is intimately related to the formation of duct structure and its maintenance.

Report

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

    (10 results)

All 2006 2005 2002 2001 2000

All Journal Article (10 results)

  • [Journal Article] Expression of keratinocyte growth factor receptor correlates with Expansive growth and early stage of gastric cancer.2006

    • Author(s)
      T.Matsunobu, T.Ishiwata, M.Yoshino, M.Watanabe, et al.
    • Journal Title

      INTERNATIONAL JOURNAL OF ONCOLOGY 28

      Pages: 307-314

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of Keratinocyte Growth Factor Receptor Correlates with Expansive Growth and Early Stage of Gastric Cancer.2006

    • Author(s)
      Matsunobu Tetsuro, Toshiyuki Ishiwata, Masanori Yoshino, Masanori Watanabe, Mitsuhiro Kudo, Koshi Matsumoto, Akira Tokunaga, Takashi Tajiri, Zenya Naito
    • Journal Title

      INTERNATIONAL JOURNAL OF ONCOLOGY 28

      Pages: 307-314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of keratinocyte growth factor receptor correlates with expansive growth and early stage of gastric cancer2006

    • Author(s)
      Tetsuro Matsunobu, Toshiyuki Ishiwata, Masanori, Yashino, Masanori Watanabe
    • Journal Title

      International Journal of Oncology (掲載予定)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Keratinocyte growth factor receptor expression in normal colorectalepitherial cells and differentiated type of colorectal cancer.2005

    • Author(s)
      M.Yoshino, T.Ishiwata, M.Watanabe, et al.
    • Journal Title

      ONCOLOGY REPORTS 13

      Pages: 247-252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Keratinocyte Growth Factor Receptor Expression in Normal Colorectal Epitherial Cells and Differentiated Type of Colorectal Cancer.2005

    • Author(s)
      Masanori Yoshino, Toshiyuki Ishiwata, Masanori Watanabe, Osamu Komine, Tetsuo Shibuya, Akira Tokunaga, Zenya Naito
    • Journal Title

      ONCOLOGY REPORTS 13

      Pages: 247-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Keratinocyte growth factor receptor expression in normal colorectal epithelial cells and differentiated type of colorectal cancer2005

    • Author(s)
      Masanori Yoshino, Toshiyuki Ishiwata, Masanori Watanabe, et al.
    • Journal Title

      Oncology Reports 13

      Pages: 247-252

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Keratinocyte growth factor receptor expression in normal colorectal epithelial cells and differentiated type of colorectal cancer2005

    • Author(s)
      Masanori Yoshino, Toshiyuki Ishiwata, Masanori Watanabe, et al.
    • Journal Title

      ONCOLOGY REPORTS 13

      Pages: 247-252

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of Lumican in Human Colorectal Cancer Cells.2002

    • Author(s)
      Yue Ping Lue, Toshiyuki Ishiwata, Kiyoko Kawahara, Masanori Watanabe, Zenya Naito, Yukichi Moriyama, Yuichi Sugisaki, Goro Asano
    • Journal Title

      Pathology International 52

      Pages: 519-526

    • NAID

      50000660331

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of Fibroblast Growth Factor (FGF)-10 in Human Colorectal Adenocarcinoma Cells.2001

    • Author(s)
      Aihiko Matsuike, Toshiyuki Ishiwata, Masanori Watanabe, Goro Asano
    • Journal Title

      J Nippon Med Sch 68

      Pages: 397-404

    • NAID

      130004146576

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of Keratinocyte Growth Factor in Cancer Cells and Enterochromaffin Cells in Human Colorectal Cancer.2000

    • Author(s)
      Masanori Watanabe, Toshiyuki Ishiwata, Keiko Nishigai, Yukichi Moriyama, Goro Asano
    • Journal Title

      Pathology International 50

      Pages: 363-372

    • NAID

      10013260172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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

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