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2000 Fiscal Year Final Research Report Summary

Involvement of LIM domain proteins and Lbd2 in the lung tissue development and carcinogensis.

Research Project

Project/Area Number 11670158
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

Principal Investigator

OSADA Hirotaka  Division of Molecular Oncology, Aichi Cancer Center, Section Head, 分子腫瘍学部, 室長 (30204176)

Project Period (FY) 1999 – 2000
KeywordsLung Cancer / Oncogene
Research Abstract

We previously isolated the human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which were differentially regulated in a tissue-specific manner. To investigate this mechanism and the transcription factors involved, we isolated the LIMK2a and 2b promoters. A luciferase reporter assay of the transcriptional activity revealed positive as well as negative regulatory regions within both promoters. The co-transfection assay suggested that the transcription factor, MZF-1, might regulate the expression of the LIMK2 isoforms in a different manner. The nuclear recptor, RORα1, might also be involved in the transcriptional regulation of the LIMK2b isoform. These findings should lead to a better understanding of the possibly diverse functions of the LIMK family.
We also isolated and studied the Ldb2 gene. The Ldb2 had the strong binding specificity to nuclar LIM proteins, which were thought to be involeved in the transcriptional regulation. The expression pattern of Ldb2 and its homologue Ldb1 were studied. The Ldb2 is expressed preferentially in normal lung, while the Ldb1 expression is increased in lung cancer tissues, suggesting the differential involvement of these genes in lung carcinogensis. We also examined the status of the Ldb2 gene in lung cancer cell lines. However, we could not find any genetic alteration.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [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・19. 2305-2311 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuda,A., et al.: "Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments."American Journal of Pathology. 158・1. 87-96 (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 Research. 60・17. 4689-4692 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,T., et al.: "Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers."Oncogene. 18・30. 4295-4300 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomoto,S., et al.: "Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers."Oncogene. 18・50. 7180-7183 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomoto,S., et al.: "Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression."Gene. 236・2. 259-271 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuda, A., Osada, H., Yatabe, Y., Kozaki, K., Tatematsu, Y., Takahashi, T., Hida, T., Takahashi, T., and Takahashi, T.: "Protective function of p27^<KIP1> 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
  • [Publications] Haruki, N., Saito, H., Harano, T., Nomoto, S., Takahashi, T., Osada, H., Fujii, F., Takahashi, T.: "Molecular Analysis of the Mitotic Checkpoint Genes BUB1, BUBR1 and BUB3 in Human Lung Cancers."Cancer Letters. 162. 201-205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagisawa, K., Uchida, K., Nagatake, M., Masuda, A., Sugiyama, M., Saito, T., Yamaki, K., Takahashi, T., and Osada, H.: "Heterogeneities in the biological and biochemical functions of Smad 2 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] Haruki, N., Saito, H., Tatematsu, Y., Konishi, H., Harano, T., Masuda, A., Osada, H., Fujii, Y., and Takahashi, T.: "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] Haruki, N., Yatabe, Y., Travis, W.D., Nomoto, S., Osada, H., Nakamura, S., Nakao, A., Fujii, Y., and Takahashi, T.: "Homo- and heterogeneity within high-grade neuroendocrine tumors of the lung."Jpn. J.Cancer Res. 91. 317-323 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto, S., Haruki, N., Takahashi, T., Masuda, A., Koshikawa, T., Takahashi, T., Fujii, Y., Osada, H., and Takahashi, T.: "Search for in vivo somatic mutations in the mitotic checkpoint gene hMAD1, in human lung cancers"Oncogene. 18. 7180-7183 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto, S., Tatematsu, Y., Takahashi, T., and Osada, H.: "Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression."Gene. 236. 259-271 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, T., Haruki, N., Nomoto, S., Masuda, A., Saji, S., Osada, H., and Takahashi, T.: "Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers."Oncogene. 18. 4295-4300 (1999)

    • 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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