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1996 Fiscal Year Final Research Report Summary

MOLECULAR BIOLOGICAL APPROACHES FOR IDENTIFYING CANCER METASTASIS-RELATING GENES

Research Project

Project/Area Number 07670260
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKANAZAWA MEDICAL UNIVERSITY

Principal Investigator

TANINO Mikio  KANAZAWA MEDICAL UNIVERSITY,DEPARTMENT OF PATHOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (60135051)

Co-Investigator(Kenkyū-buntansha) TATSUKA Masaaki  HIROSHIMA UNIVERSITY,DEPARTMENT OF REGULATORY RADIOBIOLOGY,ASSOCIATE PROFESSOR, 原爆放射能医学研究所, 助教授 (50216991)
OTA Takahide  KANAZAWA MEDICAL UNIVERSITY,DEPARTMENT OF PATHOLOGY,ASSISTANT PROFESSOR, 医学部, 講師 (10152141)
Project Period (FY) 1995 – 1996
Keywordscancer metastasis / oncogene / ras / src / expression cloning / cell motility / early embryogenesis / metalloprotease
Research Abstract

To identify cancer metastasis-related genes, we established a recipient cell (1-1ras 1000 originated from BALB/c 3T3 A31-1-1 clonal variant) system by utilizing the calcium phosphate-mediated genomic DNA transfer method. By using genomic DNAs from several human tumor cells, we detected an activity to confer metastatic phenotype to the nonmetastatic recipient cells upon the DNA transfection.
In another approach, we found that v-src-transformed BALB/c 3T3 A31-1-1 cells were highly metastatic whereas activated ras-transformed cells were nonmetastatic. It is supposed that src related-signal transduction cascade (s) are involved in the induction of metastatic ability. To identify this cascade (s), we examined the expression and the activity of membrane-type matrix metalloprotease (MT-MMP), known as a key enzyme to degradiate extracellular matrix protein and also known as a metastasis-related molecule. MT-MMP were not different between ras- and src-transformed A31-1-1 cells in culture, but there observed the increased expression and activity of MMP and MT-MMP in vivo tumor mass in src-transformed cells comparing to ras-transformed cells. This suggests that there is an apparent metastasis-inducing signal transduction system specific to in vivo.
Furthermore, we investigated the expression of MT-MMP during the development of mouse embryo with special attention to the neural crest cells. It was observed that the post-transcriptional regulation of the expression of MT-MMP were associated with the migration of these cells. We assume that the cell migration and tissue remodeling during development are suitable models for elucidating the mechanism of cancer metastasis.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Ota,T.: "CD44 participates in the tumor cell adhesion to endothelial cells in the experimental metastatic process in B16BL6 melanoma cells." Anticancer Res.15(4). 1215-1219 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatsuka,M.: "Electroporation-mediated transfection of mammalian cells with crude plasmid DNA preparations." Genetic Analysis : Biomolecular Engineering. 12(2). 113-117 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsui,T.: "Reduced sialylation of peanut agglutinin-binding sugar chains on CD44 associated with enhanced adhesiveness to endothelial cells and experimental metastatic ability in B16BL6 melanoma cells." J. Kanazawa Medical University. 20(2). 194-204 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatsuka,M.: "Structural organization of mouse DNA repair gene,N-methylpurine-DNA glycosylase." DNA and Cell Biol.14(1). 37-45 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terada,Y.: "Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation." Nature. 376(6538). 358-362 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木利光: "癌転移をめぐって" 癌治療・今日と明日. 17(2). 4-14 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 泉忠秀: "N-メチルプリンDNAグリコシラーゼ(MPG)の基質特異性とその遺伝子構造" 医学の歩み. 175(3). 220-222 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 達家雅明: "癌細胞の悪性形質発現カスケード" Molec. Med.(代謝). 32(11). 1211-1231 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatsuka,M.: "Different metastatic potentials of ras-and src-transformed BALB/c 3T3 A31 variant cells." Mol. Carcinogenesis. 15(4). 300-308 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 達家雅明: "ローンリンカーを用いたPCR法によるcDNAライブラリーの作成." 放射線生物研究. 31(2). 136-149 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ota,T.: "G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells." Life Sci.60(2). 358-362 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ota,T.: "Inhibition of metastasis by a dialysable factor in fetal bovine serum in B16 melanoma cells." Cancer Lett.110(1-2). 201-205 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano,T.: "Benzyl-α-GalNAc inhibits sialyation of O-glycosidic sugar chains on CD44 and enhances experimental metastatic capacity in B16BL6 melanoma cells." Anticancer Res.16(6B). 3577-3584 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatsuka,M.: "BALB/c 3t3 tarnsformed cell line suitable for transfection assay of metastasis inducing genes." Int.J.CANCER. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 横田淳: "「分子生物学的アプローチによる癌研究プロトコール」" 羊土社, 263 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 清木元治: "「癌転移の分子医学」" 羊土社, 153 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ota, T.: "CD44 participates in the tumor cell adhesion to endothelial cells in the experimental metastatic process in B16BL6 melanoma cells." Anticancer Res. 15 (4). 1215-1219 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "Electroporation-mediated transfection of mammalian cells with crude plasmid DNA preparations." Genetic Analysis : Biomolecular Engineering. 12 (2). 113-117 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsui, T.: "Reduced sialylation of peanut agglutinin-binding sugar chains on CD44 associated with enhanced adhesiveness to endothelial cells and experimental metastatic ability in B16BL6 melanoma cells." J.Kanazawa Medical University. 20 (2). 194-204 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "Structural organization of mouse DNA repair gene, N-methylpurine-DNA glycosylase." DNA and Cell Biol.14 (1). 37-45 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terada, Y.: "Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation." Nature. 376 (6538). 358-362 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, T.: "Current advances of the study for cancer metastasis." Cancer Therapy : Today and Future. 17 (2). 4-14 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumi, T.: "Substrate specificity and gene structure of N-Methylpurine-DNA-glycosylase (MPG)." Advances in Medicine. 175 (3). 220-222 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "Cellular signaling cascade for the expression of metastatic phenotype in cancer cells." Molec.Med.32 (11). 1211-1231 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "Different metastatic potentials of ras- and src-transformed BALB/c3T3 A31 variant cells." Molecular Carcinogenesis. 15 (4). 300-308 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "Method for the construction of cDNA library by lone-linker PCR method." Radiat.Biol.Res.Commun.31 (2). 136-149 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ota, T.: "G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells." Life Science. 60 (2). 358-362 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ota, T.: "Inhibition of metastasis by a dialysable factor in fetal bovine serum in B16 melanoma cells." Cancer Lett.110 (1-2). 201-205 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, T.: "Benzyl-alpha-GalNAc inhibits sialylation of O-glycosidic sugar chains on CD44 and enhances experimental metastatic capacity in B16BL6 melanoma cells." Anticancer Res.16 (6B). 3577-3584 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: "BALB/c 3T3 transformed cell line suitable for transfection assay of metastasis inducing genes." Int.J.Cancer. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: in vitro assay system for studying cancer metastasis In : Protocols for Molecular Biological Approaches in Cancer Biology (ed.by J.Yokota & T.Yamamoto). Yodo-sha, Tokyo, 200-210 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuka, M.: Cancer metastasis and signaling molecules In : Molecular Medicine for Cancer Metastasis (ed.by Seiki, M). Yodo-sha, Tokyo, 136-149 (1996)

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

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Published: 1999-03-09  

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