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Endometrial carcinoma arid gene mutation in relation to its carcinogenesis and prognosis

Research Project

Project/Area Number 12671627
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKitasato University

Principal Investigator

KURAMOTO Hiroyuki  Kitasato University School of Allied Health Sciences, Professor, 医療衛生学部, 教授 (80050491)

Co-Investigator(Kenkyū-buntansha) IMAI Manami  Kitasato University School of Medicine, Fellow, 医学部, 助手 (00276073)
JOBO Toshiko  Kitasato University School of Medicine, Assistant Prof., 医学部, 講師 (80110873)
WATANABE Jun  Kitasato University School of Medicine, Assistant Prof., 医学部, 講師 (10201188)
HATTORI Manabu  Kitasato University School of Allied Health Sciences, Fellow, 医療衛生学部, 助手 (60276186)
KANAI tadayuki  Kitasato University School of Medicine, Fellow, 医学部, 助手 (10276074)
佐藤 倫也  北里大学, 医学部, 助手 (20235427)
大野 英治  北里大学, 医療衛生学部, 助教授 (40276176)
秦 宏樹  北里大学, 医学部, 講師 (30146451)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsendometrial cancer / cell cycle / p53 transfection / VEGF / cyclin / p27 / PTEN / skp2 / 子宮内膜癌 / 子宮内膜増殖症 / 子宮内膜 / P27 / SKP-2 / P-14^<ARF> / P53遺伝子導入 / cyclin E / cyclin D1 / 細胞周期関連因子 / 予後因子 / cdk-2 / Ki-67 / p53
Research Abstract

The aim of the study is to clarify the correlation of gene mutation and its expression with endometrial carcinoma in relation to carcinogenesis and prognosis of the tumor. The materials are the surgical histology specimens and cell lines in vitro.
1) VEGF expression is correlated with p53 expression. When wild p53 gene was transfected into p53-mutated HEC-50B cells, VEGF expression was down regulated.
2) P53 expression was elevated in p53-mutated cells and labeling index more than 45% indicated existence of the mutation.
3) Expressions of cell cycle regulators, including Ki-67, Cyclins E, D1, A and PTEN were correlated with those of higher-grade endometrial carcinoma, whereas p14^<ARF> was inversely higher in low grade. Expressions of almost all regulators were correlated from each other. In hyperplasia, cyclin D1, A and PTEN were expressed more intensively than normal endometrium, but less than carcinoma. In contrast, cyclin E was not expressed in hyperplasia.
4) P27 did not express in proliferative phase, but in secretary phase. In carcinomas, it expressed more intensively in higher grade, seemingly loosing growth-suppressive function. Skp2, inactivating factor of p27, was activated in high-grade carcinoma. In well-differentiated carcinoma cells (HEC-265) that possess PR elevated p27, when progestin was given, preserving the reactivity of normal endometrium. In effective group of patients who had progestin therapy, p27 expression was persistent after 13 weeks of the therapy. P27 can be a predictor of effectiveness for progestin therapy.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Fujisawa T, Watanabe J, Akaboshi M, Ohno E, Kuramoto: "Immunohistochemical study on VEGF expression in endometrial carcinoma-comparison with p53 expression, angiogenesis and tumor histologic grade"J. Cancer Res. Clin. Oncol.. 127. 668-674 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanai T, Watanabe I, Kamata Y, Hamano M, Kuramoto H: "Stimuratory effect of medroxyprogesterone acetate on p27 protein in endometrial cancer cells"Kitasto Med.. 31. 392-397 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyushima N, Watanabe J, Hata H, Jobo T, Kameya T, Kuramoto H: "Expression of cyclin A protein in normal endometrium endometrial hyperplasia and adenocarcinoma-Its correlation with proliferative activity and clinicopathological variables"J. Cancer Res. Clin. Oncol.. 128. 307-312 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe J, Sato H, Kanai T, Kamata Y, Jobo T, Hata H, Fujisawa T, Ohno E, Kuramoto H.: "Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus"British J. Cancer. 87. 81-85 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujisawa T, Watanabe T, Kamata Y, Hamano M, Hata H, Kuramoto H.: "Effect of P53 transfection on vascular endothelial growth factor expression in endometrial cancer cells"Exper. Molecular Pathol.. 74. 276-281 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato N, Watanabe T, Jobo T, Nishimura Y, Fujisawa T, Kamata Y, Kuramoto H.: "Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance"J Cancer Res. Clin. Oncol.. 129. 222-226 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuramoto H., Nishida M.et al.: "Cell and molecular Biology of endometrial Carcinoma"Springer-Verlag (Ed. Kuramoto H & Nishida M). 319 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujisawa, T., Watanabe, J., Akaboshi, M., Ohno, E. & Kuramoto, H.: "Immunohistochemical study on VEGF expression in endometrial carcinoma - Comparison with p53 expression, angiogenesis and tumor histologic grade"J.Cancer Res.Clin.Oncol.. 127. 668-674 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanai T., Watanabe J., Kamata Y., Hamano M. & Kuramoto H.: "stimulatory effect of medroxyprogesterone acetate on p27 protein in endometrial cancer cells"Kitasato Med. 31(6). 392-397 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kyushima, N., Watanabe, J., Hata, H., Jobo, T., Kameya, T. & Kuramoto, H.: "Expression of cyclin A protein in normal endometrium, endometrial hyperplasia and adenocarcinoma - Its correlation with proliferative activity and clinicopathological variables"J.Cancer Res.Clin.Oncol.. 128. 307-312 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe, J., Sato, H., Kanai, T., Kamata, Y., Jobo, T., Hata, H., Fujisawa, T., Ohno, E. & Kuramoto, H.: "Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus"British J.Cancer. 87. 81-85 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujisawa, T., Watanabe, J., Kamata, Y., Hamano, M., Hata, H. & Kuramoto, H.: "Effect of p53 transfection on vascular endothelial growth factor expression in endometrial cancer cells"Exper Molecul Pathol. 74(3). 276-281 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kato, N., Watanabe, J., Jobo, T., Nishimura, Y., Fujisawa, T. Kamata, Y. & Kuramoto, H.: "Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance"J Ca Res Clin Oncol. 129. 222-226 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanai T., Watanabe J., Kamata Y., Hamano M., Kuramoto H: "Stimulatory effect of medroxy progesterone acetate on p27 protean in endometrial cancer cells"Kitasato Med.. 31・6. 392-397 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kyushima N., Watanabe J., Hata H., Jobo T., Kameya T., Kuramoto, H: "Expression of cyclin A protein in normal endometrium endometrial hyperplasia and adenocarcinoma -its correlation with proliferative activity and clinicopathological variables"J Cancer Res. Clin. Oncol. 128. 307-312 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe J., Sato H., Kanai T., Kamata Y., Jobo T., Hata H., Fujisawa T., Ohno E., Kuramoto H: "Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus"British J Cancer. 87. 81-85 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujisawa T., Watanabe J., Kamata Y., Hamano M., Hata H., Kuramoto H: "Effect of p53 translation on vascular endothtial growth factor expression in endometrial cancer cells"Exper. Molecul. Pathol. (in print).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato N., Watanabe J., Jobo T., Nishimura Y., Fujisawa T., Kamata Y., Kuramoto H: "Immune his to chemical expression of cyclin E in endometrial (adenocarcinomal endometrioid type) and its clinico pathological signiticance"J. cancer Res. clin. Oncol. (in print).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuramoto H., Nishida M: "cell and molecular biology of endometrial carcinoma"Springer-Verlag (in print).

    • Related Report
      2002 Annual Research Report
  • [Publications] Imai M., Tobo T., Sato R., Kawaguchi M., Kuramoto: "Medroxy progesterone acetate Therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus"Europ.J.Gynuecol.Oncol.. 22(3). 217-220 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsusima Nisii M., Kuramoto H., Nakamura Y.et al.: "Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN"Cancer Res.. 61. 3741-3749 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujisawa T., Watanabe J., Akaboshi M., Ohno E., Kuramoto H.: "Immunohistochemical study on VEGF expression in endometrial carconoma-comparison with p53 expression, angrogenesis"J.Cancer Res.Clin.Oncol.. 127. 668-674 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tobo T., Kawaguchi M., Kuramoto H.: "Treatment for complex atypical hyperplasia of the endometrium"Europ.J.Gynaec.Oncol.. 22(5). 365-368 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohkawara S.Toko T,Sator R v Kuramoto H: "Comparison of endometrial carcinoma coexisting with and without endometrial hyperplasia"Europ.J Ggnaecal Oncol. 21(6). 573-577 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hattoni M.Ohni E V Kuramato H: "Immunocykochemistry of cattagenase expression in transitional cell carcinoma of the bladdes."Acta Cytol. 44(5). 771-777 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wakanata T.Sako Y.Tsuohiga B Kuramoto H V Kamaga T: "Quanlitative and quantitative assessment of modifited in siku neverse transcription chain Naction (in sita RT-PCR) method"Acta Histochem Cytochem. 32(5). 423-430 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hata H.Hamano M.Wakanate J.V Kuramoto H: "Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells."Oncology. 55(suppl 1). 35-44 (1995)

    • Related Report
      2000 Annual Research Report
  • [Publications] 蔵本博行,上坊敏子,秦宏樹 他: "子宮体部の悪性腫瘍"総編集・武谷雄二,担当編集・蔵本博行.中山書店. 350 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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