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2000 Fiscal Year Final Research Report Summary

Mechanism of abnormality in p27^<K1P1> expression in human lung cancer and its therapeutic application

Research Project

Project/Area Number 11670159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

MASUDA Akira  Aichi Cancer Center Research Institute, Division of Molecular Oncology, Senior Researcher, 分子腫瘍学部, 主任研究員 (50157202)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Takashi  Aichi Cancer Center Research Institute, Division of Molecular Oncology, Research Head, 分子腫瘍学部, 部長 (50231395)
HIDA Toyoaki  Aichi Cancer Center Research Institute, Research Institute, Researcher, 研究所, 研究員 (80250249)
Project Period (FY) 1999 – 2000
KeywordsLung Cancer / p27^<K1P1> / Small Cell Lung Cancer / Cell Cycle / Apoptosis
Research Abstract

A previous study of ours unexpectedly found that in contrast to frequent reduction in non-small cell lung cancer (NSCLC) in association with poor prognosis, high expression of the p27^<K1P1> cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), which represent the most aggressive form of lung cancer. This observation suggested the possibility that highly expressed p27^<K1P1> in SCLC may be non-functional, possibly due to multiple genetic defects in this tumor type. Biochemical analyses, however, revealed that p27^<K1P1> in SCLC is functional aas a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient inhibition of cyclin-CDK kinase activities. Interestingly, we could show that induction of p27^<K1P1> confers on SCLC cells the ability to survive under culture conditions unfavorable for cell growth such as a lack of nutrients and hypoxia. Subsequent transfection experiments with p27^<K1P1> supported this notion. These obsevations suggest that high expression of p27^<K1P1> in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kozaki,K. et al.: "In vivo selected human lung cancer cell line H460-LNM35 consistently exhibits lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Res.. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagisawa,K. el al.: "Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers."Oncogene. 19. 2305-2311 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yatabe,Y. et al.: "Topographical distributions of allelic loss in individual non-small cell lung cancers."Am.J.Pathol.. 157. 985-993 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hida,T. et al.: "Cyclooxygenase (COX)-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin.Cancer Res.. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Haruki,N. et al.: "Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer."Cancer Res.. 60. 4689-4692 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuda,A. et al.: "protective function of p27^<KIP1> again apoptosis in small cell lung cancer cells in unfavorable microenvironments."Am.J.Pathol.. 158. 87-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kozaki, K.et al.: "In vivo selected human lung cancer cell line H460-LNM35 consistently exhibits lymphogenous metastasis via both subcutaneous and orthotopic propagation."Cancer Res.. 69. 2535-2540 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagisawa, K.et al.: "Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers."Oncogene. 19. 2305-2311 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yatabe, Y.et al: "Topographical distributions of allelic loss in individual non-small cell lung cancers."Am. J.Pathol.. 157. 985-993 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hida, T.et al.: "Cyclooxygenase (COX)-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines."Clin. Cancer Res.. 6. 2006-2011 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Haruki, N.et al: "Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer."Cancer Res.. 60. 4689-4692 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masuda, A.et al: "Protective function of p27^<K1P1> against apoptosis in small cell lung cancer cells in unfavorable microenvironments."Am. J.Pathol.. 158. 87-96 (2001)

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

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Published: 2002-03-26  

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