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2001 Fiscal Year Final Research Report Summary

Functional analysis of α-fetoprotein by genetically engineered mice

Research Project

Project/Area Number 12670127
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHokkaido University

Principal Investigator

NISHI Shinzo  Hokkaido Univ.,Grad. School of Med., Prof., 大学院・医学研究科, 教授 (20001894)

Co-Investigator(Kenkyū-buntansha) KOYAMA Yoshikazu  Hokkaido Univ.,Grad. School of Med., Inst., 大学院・医学研究科, 助手 (90186841)
NAKABAYASHI Hidekazu  Hokkaido Univ.,Grad. School of Med., Inst., 大学院・医学研究科, 助手 (10033383)
SAKAI Masaharu  Hokkaido Univ.,Grad. School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (50162269)
Project Period (FY) 2000 – 2001
Keywordsα-fetoprotein / immunosupression / auto-imune doseases / T-Cell / hepatocellular cacinoma / transgenic mice
Research Abstract

α-fetoprotein (AFP) is a serum protein in appreciable amounts in fetal but not in adult serum. However, serum AFP is frequently elevated in patients with hepatocellular carcinomas and yolk sac tumors. Numerous studies have suggested that immunomodulation may be one of the biological functions of AFP. To clarify the biological function of the AFP in vivo, we have established two transgenic mice, which have human and mouse AFP genes under the control of β-actin promoter. In these mice, ubiquitous expressions of AFP were observed. Using these mice, we have been analyzed experimental autoimmune diseases, such as arthritis, autoimmune thyroiditis and experimental allergic encephalomyelitis. We have showed that development of all these experimental autoimmune diseases were significantly suppressed in AFP produced transgenic mice compared with wild mice. The development of experimental allergic encephalomyelitis of the mouse AFP producing mice was more suppressed than the mouse producing human AFP.
Monoclonal antibodies (MAbs) against human AFP have been used in a variety of procedures including immuno assay, immunoscintigraphy and immunotherapy. A number of MAbs have been produced, but their epitopes remain to be defined. We have analyzed 36 MAbs against human AFP using recombinant AFP peptides and synthesized overlapping octapeptides. Epitopes of 13 MAbs were mapped in domain I and 17 were on domain II. The epitope of one of the MAb, AFY6, was localized on C^<175>KAENAVE^<182>.
We also analyzed the AFP gene regulation. Glucocorticoid inhibit rodent AFP gene activity but stimulate expression of the human AFP. The glucocorticoid induction of human AFP is mediated by a GRE on the AFP gene promoter and corresponding element of the mouse is a binding site of the HNF4, a hepatocyte enriched transcription factor. The interaction of the glucocorticoid receptor and HNF4 may account for this opposite effects.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Onodera, S., Kaneda, K., Mizue, Y., Koyama, Y., Fujinaga, M. et al.: "Macrophage Migration Inhibitory Factor (MIF) up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis"J. Biol. Chem.. 275. 444-450 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本律, 小山芳一, 石倉浩, 金内優典, 藤野敬史 他: "子宮体部原発肝様腺癌と、それにより産生されるalpha-fetoproteinの検討"産科と婦人科. 67. 384-388 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Huang, K., Serria, M.S., Nakabayashi, H., Nishi, S., Sakai, M.: "Molecular cloning and functional characterization of the mouse mafB gene"Gene. 242. 419-426 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koyama, N., Nishihira, J., Nakabayashi, H., Nishi, S. et al.: "Aneuploidy of sex chromosomes in basal cell carcinoma : Its clonality and involvement in the development of carcinogenesis"Int. J. Oncol.. 16(1). 15-23 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imaki J, Onodera H, Tsuchiya K, Imaki T, Mochizuki T, et al.: "Developmental expression of maf-1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry"Biochem Biophys Res Commun.. 272. 777-782 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kang, Q., Matsuura, E., Sakamoto, T., Sakai, M., Nishi, S.: "Analysis of epitopes of mouse monoclonal antibodies against human alpha-fetoprotein"Tumor Biol.. 22. 254-261 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakai, M., Serria, M.S., Ikeda, Yoshida, K., Imaki, J., Nishi, S.: "Regulation of c-maf gene expression by Pax6 in cultured cells"Nucleic Acids Res.. 29. 1228-1237 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakabayashi, H., Koyama, Sakai, M., Li, H.M., Wong, N.C.W., Nishi, S.: "Glucocorticoid Stimulates Primate but Inhibits Rodent α-Fetoprotein Gene Promoter"Biochem Biophys Res Cormmun. 287. 160-172 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asakura T, Hasizume, Y, Tashiro, Ki, Searashi Y, Ohkawa K, Nishihira J, Sakai, M., Shibasaki T: "Suppression of GST-P by treatment with glutathione-doxorubicin conjugate induces potent apoptosis in rat hepatoma cells"Int J Cancer. 94. 171-177 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida K, Kim JI, Imaki J, Hiromi I, Nishi S, Matsuda H, Haradal T, et al.: "Proliferation in the posterior region of the lens of c-maf-/-mice"Current Eye Research. 23. 116-119 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujikawa, K., Inoue, Y., Sakai, M., Koyama, Y., Nishi, S., et al.: "Vav3 is regulated during cell cycle and effects cell division"Proc Natl. Acad. Sci, USA. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda, H., Serria, MS., Kakizaki, I., Hatayama, I., Satoh, K., et al.: "Activation of Mouse Pi-class Glutathione S-Transferase gene by Nrf2 and Androgen"Biochemical J.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koyama, N., Nishihira, J., Nakabayashi, H., Nishi, S., Hoshi, N., Fujimoto, S., Shimizu, M., Yoshiki, T., Sugihara, T.: "Aneuploidy of sex chromosomes in basal cell carcinoma: Its clonality and involvement in the development of carcinogenesis"Int. J. Oncol.. 16. 15-23 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, R., Koyama, Y., Ishikura, H., Kaneuchi, M., Fujino, T., Sagawa, T., Sakuragi, N., Taketa, K., Nishi, S., Fujimoto, S.: "Study on alpha-fetoprotein derived from endometrial hepatoid adenocarcinoma."Obstetrics and Gynecology (San-ka to Fujinn-ka). 67. 384-388 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onodera, S., Kaneda, K., Mizue, Y., Koyama, Y., Fujinaga, M., Nishihira, J.: "Mecrophage Migration Inhibitory Factor (MIF) up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis."J. Biol. Chem.. 275. 444-450 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Huang, K., Serria, M.S., Nakabayashi, H., Nishi, S., Sakai, M.: "Molecular cloning and functional characterization of the mouse mafB gene"Gene. 242. 419-426 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Imaki J., Onodera, H., Tsuchiya, K., Imaki, T., Mochizuki, T., Mishima, T., Yamashita, K., Yoshida, K., Sakai, M.: "Developmental expression of maf-1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry"Biochem Biophys Res Commun. 272. 777-782 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kang, V., Matsuura, E., Sakamoto, T., Sakai, M., Nishi, S.: "Analysis of epitopes of mouse monoclonal antibodies against human alpha-fetoprotein."Tumor Biol. 22. 254-261 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakai, M., Serria, M.S., Ikeda, Yoshida, K., Imaki, J., Nishi, S.: "Regulation of c-maf gene expression by Pax6 in cultured cells."Nucleic Acids Res.. 29. 1228-1237 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakabayashi, H., Koyama, Sakai, M., Li, H.M., Wong, N.C.W., Nishi, S.: "Glucocorticoid Stimulates Primate but Inhibits Rodent α-Fetoprotein Gene Promoter"Biochem Biophys Res Commun.. 287. 160-172 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asakura, T., Hashizume, Y., Tashiro, Ki, Searashi, Y., Ohkawa, K., Nishihira, J., Sakai, M., Shibasaki, T.: "Suppression of GST-P by treatment with glutathione-doxorubicin conjugate induces potent apoptosis in rat hepatoma cells"Int J Cancer. 94. 171-177 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida, K., Kim, JI, Imaki, J., Hiromi, I., Nishi, S., Matsuda, H., Haradal, T., Harada, C., Ohno, S., Sakai, M.: "Proliferation in the posterior region of the lens of c-maf-/-mice."Current Eye Research. 23. 116-119 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujikawa, K., Inoue, Y., Sakai, M., Koyam. Y., Nishi, S., Funada, R. Alt, F. W., Swat, W.: "Vav3 is regulated during cell cycle and effects cell division."Proc Natl. Acad. Sci, USA. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda,H., Serria, MS. Kakizaki, I., Hatayama, I., Satoh, K., Tsuchida. S., Muramatsu, M., Nishi, S., Sakai, M.: "Activation of Mouse Pi-class Glutathione S-Transferase gene by Nrf2 and Androgen."Biochemical J. (in press). (2002)

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

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Published: 2003-09-17   Modified: 2021-12-09  

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