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Study of mechanisms of the highly metastatic feature using human lung cancer sublines with highly metastatic property established

Research Project

Project/Area Number 11670598
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNippon Medical School

Principal Investigator

GEMMA Akihiko  Medical School Lecturer, 医学部, 講師 (20234651)

Co-Investigator(Kenkyū-buntansha) UEMATSU Kazutsugu  Assistant Professor, 医学部, 助手 (10297880)
SHIBUYA Masahiko  Associate Professor, 医学部, 助教授 (50142534)
KUDOH Shoji  Professor, 医学部, 教授 (40256912)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsLung Cancer / Metastasis / Microarray / Macroarray / Gene Expression
Research Abstract

A better understanding of the key factors of metastasis may be useful for designing new molecular targets of therapy. In order to identify these factors, we established two highly metastatic human lung adenocarcinoma cell lines in an experimental metastasis model by repeated inoculation in nude mice and compared the expression profiles of two subpopulations of an adenocarcinoma cell line with high metastatic potential, with the parent cell line, using cDNA arrays ; microarray and macroarray. The expression of 5 genes was found to be significantly enhanced or reduced in the highly metastatic subpopulations by microarray. The genomic structure of these genes will be detrmined. The expression of matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor-1 (PAI-1), carcinoembryonic antigen (CEA), Fas ligand and etc.were upregulated or downregulated in the highly metastatic subpopulations. The differential expression of these genes was confirmed by Northern blot analysis or reverse transcription-polymerase chain reaction (RT-PCR). Altered expression of these genes seems to promote the highly metastatic phenotype in these function. To determine whether the change in p16INK4 methylation status and the genomic status of hBUB1, hMAD2, Insulin-like growth factor 2 receptor genes occurs during metastasis of primary lung cancers, we also analyzed the primary and metastatic tumor tissues and normal lung samples from 30 cases of advanced lung cancer with distant metastasis. The results of this study indicate that tumor cells in which the p16INK4 gene has been inactivated by hypermethylation of the promoter region could have an advantage in metastasis in non-small cell lung cancers. The differential expression of the gene was not detected among subpopulations with high metastatic potential of the cell line and the parent line. The expression of the p16INK4 gene did not seem to be involved in the highly metastatic phenotype in this cell line.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Akihiko Gemma: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers."Lung Cancer. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gemma A.: "Somatic mutation of the hBUB1 mitotic checkpoint gene in primary lung cancer."Genes chromosomes and cancer. 29(3). 213-218 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seike M.,: "Increase in the frequency of p16INK4 Gene Inactivation by Hypermethylation in Lung Cancer juring the Process of Metastasis and its Relation to the Status of p53."Clinicl Cancer Research. 6. 4307-4313 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gemma A.: "Mutation analysis of the gene encoding the human mannose 6-phosphate/insulin-like growth factor 2 receptor (M 6P/IGF2R) in human cell lines resistant to growth inhibition by transforming growth factor b1 (TGF b1)."Lung Cancer. 30. 91-98 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takenaka K.: "ALTERED EXPRESSION AND FUNCTION OF b1 INTEGRINS IN A HIGHLY METASTATIC HUMAN LUNG ADENOCARCINOMA CELL LINE."Internatioal Journal of Oncology. 17. 1187-1194 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiko Gemma.: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers."Lung Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gemma A.: "Somatic mutation of the hBUB1 mitotic checkpoint gene in prim ary lung cancer."Genes chromosomes and cancer. 29(3). 213-218 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seike M.: "Increase in the frequency of p16INK4 Gene Inactivation by Hypermethylation in Lung Cancer during the Process of Metastasis and its Relation to the Status of p53."Clinical Cancer Research. 6. 4307-4313 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gemma A.: "Mutation analysis of the gene encoding the human mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in human cell lines resistant to growth inhibition by transforming growth factor b1 (TGF b1)."Lung Cancer. 30. 91-98 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takenaka K.: "ALTERED EXPRESSION AND FUNCTION OF b1 INTEGRINS IN A HIGHLY METASTATIC HUMAN LUNG ADENOCARCINOMA CELL LINE."International Journal of Oncology. 17. 1187-1194 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akihiko Gemma: "Genomic Structure of the Human MAD2 Gene and Mutation Analysis in Human Lung and Breast Cancers."Lung Carcer,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Gemma A.: "Somatic mutation of the hBUB1 mitotic checkpoint gene in primary lung cancer."Genes chromosomes and cancer. 29(3). 213-218 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seike M.: "Increase in the frequency of p16INK4 Gene Inactivation by Hypermethylation in Lung Cancer during the Process of Metastasis and its Relation to the Status of p53."Clinicl Cancer Research,. 6. 4307-4313 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gemma A.: "Mutation analysis of the gene encoding the human mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in human cell lines resistant to growth inhibition by transforming growth factor b1 (TGF b1)."Lung Cancer,. 30:. 91-98 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takenaka K.: "ALTERED EXPRESSION AND FUNCTION OF b1 INTEGRINS IN A HIGHLY METASTATIC HUMAN LUNG ADENOCARCINOMA CELL LINE."Internatioal Journal of Oncology,. 17. 1187-1194 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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