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2002 Fiscal Year Final Research Report Summary

Analysis of molecular mechanism in endometrial cancer development.

Research Project

Project/Area Number 12557138
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

KATO Kiyoko  Kyushu University, Medical Institute of Bioregulation Kyushu Univ. Lecturer, 生体防御医学研究所, 講師 (10253527)

Co-Investigator(Kenkyū-buntansha) WAKE Norio  Kyushu University, Medical Institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (50158606)
Project Period (FY) 2000 – 2002
KeywordsRas / ER / tumorigenicity / Senescence
Research Abstract

We previously reported that enhanced transcriptional activation of estrogen receptorα(ERα) contributed to [^<12> Val] K-Ras mediated NIH3T3 cell transformation. Functional inactivation of ERα by a dominant negative mutant of ERα (DNER) in the presence of activated K-Ras 4B mutant arrested the cell cycle at G0/G1, subsequently provoking replicative cell senescence, finally abrogating tumorigenic potential. p53-dependent up-regulation of p21 was implicated in this cell senescence induction. Alterations in the MDM2 protein in response to DNER accounted for this p21-mediated cell senescence induction. An oncogenic K-Ras 4B mutant significantly increased MDM2 proteins coprecipitated with p53, and suppressed p53 transcriptional activity. In turn, DNER exerted its function to decrease MDM2 proteins coprecipitated with p53, followed by the stimulation of p53 activity in the presence of the oncogenic K-Ras 4B mutant. In addition, overexpression of wild type ERα in NIH3T3 cells resulted in the significant increase in the MDM2 protein level and the resultant suppression of p53 transcriptional activity. Finally, we demonstrated that c-Jun expression overcame the suppression and resultant enhancement of p21 protein level in response to DNER. The data imply that the ERα-APl pathway activated by oncogenic K-Ras 4B mutant contributes to the NIH3T3 cells' transformation by modulating p53 transcriptional activity through MDM2.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Ueoka Y et al.: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras-mediated pathway"Br.J.Cancer. 84,4. 891-899 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terao Y et al.: "Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecological cancer cells"International Journal of cancer. 94. 257-267 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato K et al.: "Contribution of estrogen receptora (ERα) to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway"J.Biol.Chem. 277,13. 11217-11224 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato K et al.: "Contribution of estrogen receptor α and progesterone receptor-B to oncogenic K-Ras-mediated NIH3T3 cell transformation"Cell and Molecular Biology of Endometrial Carcinoma : Springer-Verlag Tokyo. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueoka Y et al.: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras mediated pathway"Molecular and cellular endocrinology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueoka Y et al: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras-mediated pathway."British Journal of Cancer. 84,4. 891-899 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terao Y et al: "Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecological cancer cells."International Journal of cancer. 94. 257-267 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato K et al: "Contribution of estrogen receptor aα (ERα) to oncogenic K-Ras-mediated NIH3T3 cell transformation and its implication for escape from senescence by modulating the p53 pathway."Journal of Biological Chemistry. 277,13. 11217-11224 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueoka Y et al: "Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras mediated pathway."Molecular and cellular endocrinology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato K et al: "Contribution of estrogen receptor α and progesterone receptor-B to oncogenic K-Ras-mediated NIH3T3 cell transformation., Cell and Molecular Biology of Endoraetrial Carcinoma(in press)"Springer-Verlag Tokyo.

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

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Published: 2004-04-14  

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