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The investigation on the expression regulation and the role on chemosensitivity of a xenobiotic enzyme GSTP1 in lung cancer.

Research Project

Project/Area Number 14570559
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionYokohama city university

Principal Investigator

MATSUSE Takeshi  Yokohama city university, medical center, professor, 医学部附属病院, 教授 (90199795)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Jun  Tokyo university, school of medicine, associate professor, 医学部, 助教授 (90188954)
ITO Takaaki  Kumamoto university, school of medicine, professor, 医学部, 教授 (70168392)
SHIRAI Akira  Yokohama city university, medical center, associate professor, 医学部附属病院, 助教授 (40244488)
増田 道明  独協医科大学, 医学部, 教授 (80199702)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordslung cencer / chemosensitivity / xenobiotic enzyme / GSTP1 / DNA methylation
Research Abstract

1.Induction of CpG island methylation of GSTP1 promoter in lung adenocarcinoma cells.
The CpG island of GSTP1 promoter was not methylated and GSTP1 was detected by immunoblotting in A549 lung adenocarcinoma cells. When we transduced the methylated oligonucleotides to these cells, methylation of the GSTP1 promoter and reduction of GSTP1 expression was induced.
2.Induction of CpG island methylation with DNA methyltransferases (DNMT)
It was observed that DNMT1, 3a, and 3b were all expressed in A549 cells. We cloned the cDNA of DNMT3b, and established a stable transfectant of DNMT3b from A549 cells. Now we check the methylation status of GSTP1 CpG island in these transfectants with bisulfite sequenting.
3.Association between GSTP1 expression and viability of lung-derived cells (including lung cancer cells)
We regulate the expression level of GSTP1 in human lung-derived fibroblast HFL-1 and A549 lung cancer cells, and investigated the role of GSTP1 on spontaneous apoptosis. Depletion of GSTP1 increased spontaneous apoptosis and necrosis in both kinds of cells. Although we investigated the mechanism of this phenomena, we found no relations between this phenomena and JNK pathway or intracellular concentration of glutathione.
4.Association between GSTP1 expression and chemosensitivity
As a pilot study, we carried out transfection of GSTP1 sense and antisense vectors to examine effects of GSTP1 on apoptosis induced by camptothecin in HeLa cells. Camptothecin-induced apoptosis was attenuated by transfection of GSTP1 sense vector in HeLa cells.
We also observed that GSTP1 depletion with siRNA increased camptothecin-induced cell death in A549 lung cancer cells.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Ishii T, Matsuse T, et al.: "Depletion of glutathione S-trasnferase P1 induces apoptosis in human lung fibroblasts."Experimental Lung Research.. 29. 523-536 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara T, Matsuse T, et al.: "Glutathione S-Transferase P1 has Protective Effects on Cell Viability against Camptothecin."Cancer Letters.. 203. 199-207 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii T, Matsuse T, et al.: "A methylated oligonucleotide induced methylation of GSTP1 promoter and suppressed its expression in A549 lung adenocarcinoma cells."Cancer Letters.. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii T, Matsuse T, et al.: "Depletion of glutathione S-trasnferase P1 induced apoptosis in human lung fibroblasts."Experimental Lung Research. 29. 523-536 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara T, Matsuse T, et al.: "Glutathione S-Transferase P1 has Protective Effects on Cell Viability against Camptothecin."Cancer Letters. 203. 199-207 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii T, Matsuse T, et al.: "A methylated oligonucleotide induced methylation of GSTP1 promoter and suppressed its expression in A549 lung adenocarcinoma cells."Cancer Letters. (accepted). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii T.: "Depletion of glutathione S-trasnferase P1 induces apoptosis in human lung fibroblasts"Experimental Lung Research. 29・7. 523-536 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hara T.: "Glutathione S-Transferase P1 has Protective Effects on Cell Viability against Camptothecin"Cancer Letters. 203・2. 199-207 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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