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A role of beta-catenin/p53 pathway on tumor cell proliferation and differenatiation of endometrial carcinoma cells

Research Project

Project/Area Number 15590313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKitasato University

Principal Investigator

SAEGUSA Makoto  Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (00265711)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsBeta-catenin / p53 / p21WAF1 / p14ARF / endometrial cancer / senescence / β-カテニン / 子宮内膜癌 / p21 / p14 / TCF4
Research Abstract

The functional consequences of β-catenin as a transcription factor are complex in a variety of tumors. To clarify roles during squamous differentiation (SqD) of endometrial carcinoma (Em Ca) cells, we investigated expression of β-catenin, as well as cyclin D1, p53, p21WAF1, and PML (promyelocytic leukemia) in 80 cases of Em Ca with SqD areas, in comparison with cell proliferation determined with reference to Ki-67 antigen positivity. The role of β-catenin-TCF-mediated transcription was also examined using Em Ca cells. In clinical cases, nuclear β-catenin accumulation was more frequent in SqD areas, being positively linked with expression of cyclin D1, p53, and p21WAF1, and inversely to Ki-67 and PML immunoreactivity. Significant correlations of nuclear β-catenin, cyclin D1, p53, and p21WAF1, were noted between SqD and the surrounding carcinoma lesions. The Ishikawa cell line, with stable or tetracycline-regulated expression of mutant β-catenin, showed an increase in expression levels of cyclin D1, p14ARF, p53, and p21WAF1 but not PML and activation of β-catenin-TCF4-mediated transcription determined by TOP/FOP constructs. The cell morphology was senescence-like rather than squamoid in appearance. Moreover, overexpressed β-catenin could activate transcription from p14ARF and cyclin D1 promoters, in a TCF4-dependent manner. These findings indicate that in Em Cas, nuclear β-catenin can simultaneously induce activation of the p53-p21WAF1 pathway and overexpression of cyclin D1, leading to suppression of cell proliferation or induction of cell senescence. However, overexpression of β-catenin alone is not sufficient for development of a squamoid phenotype in Em Ca cells, suggesting that nuclear accumulation is an initial signal for trans-differentiation.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (3 results)

All 2004

All Journal Article (3 results)

  • [Journal Article] β-catenin simultaneously induces activation of the p53-p21WAF1 pathway and overexpression of cylin D1 during squamous differentiation of endometrial carcinoma cells2004

    • Author(s)
      Saegusa m et al.
    • Journal Title

      American Journal of Pathology 164

      Pages: 1739-1749

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] β-catenin simultaneously induces activation of the p53-p21WAF1 pathway and overexpression of cylin D1 during squamous differentiation of endometrial carcinoma cells2004

    • Author(s)
      Saegusa M et al.
    • Journal Title

      Am J Pathol 164

      Pages: 1739-1749

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] β-catenin simultaneously induces activation of the p53-p21WAF1 pathway and overexpression of cyclin D1 during squamous differentiation of endometrial carcinoma cells2004

    • Author(s)
      Saegusa M et al.
    • Journal Title

      American Journal of Pathology 164

      Pages: 1739-1749

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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