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Analysis of mucin glycoproteins in the gallbladder of BK5.erbB2 transgenic mouse

Research Project

Project/Area Number 15590618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Tsukuba

Principal Investigator

SHODA Junichi  University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (90241827)

Co-Investigator(Kenkyū-buntansha) 川本 徹  筑波大学, 臨床医学系, 講師 (30282354)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsgallbladder carcinoma / animal model / mucin glycoprotein / oncogene / signal transduction / gallbladder carcinogenesis / 実験リトル
Research Abstract

The overall prognosis of gallbladder carcinoma is poor because of a high percentage of advanced cases at the time of operation and thereby a lower curability. pT2 carcinoma is limited in the gallbladder wall, and therefore a high curability as well as a better prognosis can be expected. However, the prognosis has not been necessarily good since distant recurrences are found in some cases of pT2 carcinomas. Alterations in glycosilation of mucins, such as an alteration in the site of O-glycosylation of mucin core proteins or an enhanced sialylation of carbohydrate structures, are known in the process of malignant transformation.
Mucin-type O-glycosilation is initiated by GalNAc-T isozymes and O-glycosilation in adenocarcinoma cell lines is reportedly catalyzed by GalNAc-T3. In pT2 gallbladder carcinoma, the differential expression of GalNAc-T3 in pT_2 carcinoma may modulate the malignant behavior of the carcinoma cells by affecting the biological properties of mucins due to the altered O- … More glycosilation.
Sialylated MUC1 recognized by a mAb MY.1E12 (Jpn J Cancer Res 1996;87:488-496) has been used as a marker for invasive adenocarcinomas. In pT2 gallbladder carcinoma, the high level expression of stromal localization of sialylated MY. 1E12-reactive-MUC1 at the invading sites correlates with the aggressiveness of the disease, such as the tendency to form distant metastasis.
BK5.ErbB2 transgenic mice overexpressing erbB2 develop gallbladder carcinoma at a high incidence. Recently, Muc4 (sialomucin complex) has been shown to influence erbB2 (tyrosine kinase) activity through direct interaction with the receptor and to potentiate tumor growth in mammalian carcinoma cells. Also in the transgenic mice, up-regulation of Muc4 and its interaction with erbB2 may be involved in the process of gallbladder carcinogenesis through modulation of phosphorylation of the receptor tyrosine kinase.
Thus, alterations in carbohydrate chains of carcinoma-producing mucin glycoproteins potentiate the capability of tumor invasion and/or metastasis and Muc4 may play an important role in gallbladder carcinogenesis through the activation of erbB2. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2005 2004 Other

All Journal Article (10 results) Publications (6 results)

  • [Journal Article] A novel β1,3-N-acetylglucosaminyltransferase(β3Gn-T8)2005

    • Author(s)
      Ishida, H., Shoda, J.
    • Journal Title

      FEBS Lett. 579

      Pages: 71-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel β1,3-N-acetylglucosaminyltransferase (β3Gn-T8)2005

    • Author(s)
      Ishida, H., Shoda, J.
    • Journal Title

      FEBS Lett. 579

      Pages: 71-78

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of MUC1 recognized by a monoclonal antibody2004

    • Author(s)
      Kawamoto, T., Shoda, J.
    • Journal Title

      Clin Exp Metastasis 21

      Pages: 353-362

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Aberrant expression of MUC1 recognized2004

    • Author(s)
      Shinozaki, E., Shoda, J.
    • Journal Title

      Int J Oncol 25

      Pages: 1257-1265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Mutations identified in the human multidrug resistance2004

    • Author(s)
      Kano, M., Shoda, J.
    • Journal Title

      Hepatology Res 29

      Pages: 160-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expression of UDP-N-acetyl-α-D-galactosamine-polypeptide2004

    • Author(s)
      Miyahara, N., Shoda, J.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2090-2099

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expression of MUC1 recognized by monoclonal antibody2004

    • Author(s)
      Miyahara, N., Shoda, J.
    • Journal Title

      Clin Exp Metastasis 21

      Pages: 321-324

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of UDP-N-acetyl-α-D-galactosamine-polypeptide GalNAc N-acetylgalactosaminyl transferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.2004

    • Author(s)
      Miyahara, N., Shoda, J., Kawamoto, T., Furukawa, M., Ueda, T., Todoroki, T., Tanaka, N., Matsuo, K., Yamada, Y., Kohno, K., Irimura, T.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2090-2099

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of MUC1 recognized by a monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of carcinoma of the gallbladder.2004

    • Author(s)
      Kawamoto, T., Shoda, J., Todoroki, T., Suzuki, H., Miyahara, M., Furukawa, M., Tanaka, N., Irimura, T
    • Journal Title

      Clin Exp Metastasis 21

      Pages: 353-362

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of MUC1 recognized by monoclonal antibody2004

    • Author(s)
      Suzuki, H., Shoda, J.
    • Journal Title

      Clin Exp Metastasis 21

      Pages: 321-324

    • Related Report
      2004 Annual Research Report
  • [Publications] Shoda J, et al.: "Hepatolithiasis-Epidemiology and pathogenesis update"Frontiers in Bioscience. 8. 398-409 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shoda J, et al.: "Novel mutations identified in thehuman multidrug resistance-associated protein 2 (MRP2) gene"Hepatology Research. 27. 322-325 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shoda J, et al.: "Involvement of prostaglandin E2 and its specific receptor subtype EP4 in chronic proliferative cholangitis"Clin Gastroenterol & Hepatol. 1. 285-296 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shoda J, et al.: "Genipin, an active metaboplite of a herbalmedicine Inchinko-To, enhances multidrug resistance-associated protein 2-mediated bile formation in rats"Hepatology. 39. 167-178 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyahara N, Shoda J, et al.: "Expression of UDP-N-acetyl-a-D-galactosamine-polypeptide GalNAc N-acetylgalactosaminyl transferase isozyme 3"Clin Cancer Res. 10(In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kano M, Shoda J, et al.: "Mutations identified in the human multidrug resistance P-glycoprotein 3(ABCB4) gene in patients with primary hepatolithiasis"Hepatology Research. 28(In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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