• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2003 Fiscal Year Final Research Report Summary

Regulatory mechanisms for wound-related gene expression at invasive front of Lung adenocarcinomas

Research Project

Project/Area Number 14570136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionThe University of Tokyo

Principal Investigator

NIKI Toshihiro  The University of Tokyo, Department of Human Pathology, Associate Professor, 大学院・医学系研究科, 助教授 (90198424)

Project Period (FY) 2002 – 2003
Keywordslung adenocarcinoma / inflammation / wound healing / invasion
Research Abstract

To elucidate the regulatory mechanisms for wound-related geneexpression at the invasive front of lung adenocarcinomas, the following investigations were performed:
(1)The promoter region of laminin-5 gamma2 gene spanning the 1.5kb region upstream of the transcription initiation site was PCR amplified and cloned into pGL3-luc vector. Preliminary experiment confirmed that this region controls the upregulation of laminin-5 gamma2 gene after stimulation with TGF-alpha. The results of this study showed that (a)This promoter activity is induced 20 fold by co-transfection of active MEK expression vector, whereas it is inhibited by pharmacologic MEK inhibitor: (2)The activity of laminin-5 gamma2 promoter is strongly repressed by the wild-type, but not by the mutant type, p53 gene. Subsequent analyses with serial deletion mutant of the laminin-5 promoters revealed that this regulatory mechanism is retained in promoters upstream of 0.5 kb transcription initiation site.
(2)To investigate the activation of wound-related signal transduction pathways in lung adenocarcinoma tissues, immunohistochemical analyses were performed using phospho-specific antibodies. The results showed that c-met is activated in 4/20 cases, erk in 15/20 cases, jnk in 3/20 cases, and p38 in 7/20 cases. As regards NF-kappaB, p65 and p50 subunits were positive in all the 20 cases examined, with certain populations of cancer cells showing nuclear immunoreactivities for these two proteins.
(3)The activation of c-met was further analyses in a total of 78cases of resected lung adenocarcinomas. The activation of the c-met receptor was detected in 14/78 cases (17.9%). Active form of c-met was localized at the surface of cancer cells, especially in adenocarcinomas of well differentiated type. Similar localized was observed in several lung adenocarcinoma cell lines.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Niki T et al.: "Frequent co-localization of cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas."Am J Pathol. 160. 1129-1141 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomizawa Y et al.: "Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma."Clin Cancer Res. 8. 2362-2368 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeshima AM et al.: "Modified scar grade : a prognostic indicator in small peripheral lung adenocarcinoma"Cancer. 95. 2546-2554 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takei H: "Large cell neuroendocrine carcinoma of the lung : A clinicopathologic study of eighty-seven cases."J Thorac Cardiovasc Surg.. 124. 285-292 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terasaki H: "Lung adenocarcinoma with mixed bronchiolo-alveolar and invasive components : clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization."Am J Surg Pathol. 27. 937-951 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Niki T et al.: "Frequent co-localization of cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas."Am J Pathol. 160. 1129-114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomizawa Y et al.: "Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage l lung adenocarcinoma."Clin Cancer Res. 8. 2362-2368 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeshima AM et al.: "Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma"Cancer. 95. 2546-2554 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takei H et al.: "Large cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighty-seven cases."J Thorac Cardiovasc Surg. 124. 285-292 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terasaki H et al.: "Lung adenocarcinoma with mixed bronchiolo-alveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization."Am J Surg Pahol. 27. 937-951 (2003)

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

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi