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Analysis of cell-cycle regulatory mechanisms in human hematopoietic cells

Research Project

Project/Area Number 09671092
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MOTOKURA Toru  The University of Tokyo, Faculty of Medicine Branch Hospital Assistant Professor, 医学部・附属病院分院, 助手 (00192823)

Co-Investigator(Kenkyū-buntansha) NAKAHARA Tatsutoshi  The University of Tokyo, Institute of Medical Science Professor, 医科学研究所, 教授 (20110744)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsHEMATOPOIESIS / CELL CYCLE / CYCLIN / p16INK4a / p21CIP1 / p27KIP1 / MEGAKARYOCYTE / TUMORIGENESIS / p21WAF1
Research Abstract

1) When MEG-Ols cells ceased growth and differentiated along a megakaryocytic lineage in response to TPA, p21CIP1 and p27KIP1 expression was induced and cyclin E-associated kinase was inactivated. We developed a quantitative RT-PCR for these CKIs expression and found that p2lCIP1 mRNA increased along with differentiation of any lineage. Immunohistochemistry revealed that p21CIP1 and p27KIP1 proteins were present in megakaryocytes and suggested that p27KIP1 protein was expressed in non-cycling megakaryocytes which were negative for Ki-67.
2) In liquid culture, proliferation of CD34+ cord blood cells were linked to cyclin D1 and p21 expression.
3) We proved the usefulnes of our RT-PCR assay for cyclin D1 overexpression by examining clinical specimens obetained from patients with hematological malignancies. Using the same strategy, we examined expression of CKIs including pl6INK4a, p14ARF, p21CIP1 and p27KIP1 in these specimens and hematopoietic cell lines. Aberrant expression of pl6INK4a was more frequent than p14ARF.On the contrary, p21CIP1 and p27KIP1 expression was not altered significantly. We also reported eases of cyclin D1-overexpressing mantle cell lymphoma and hairy cell leukemia.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 折井幸司: "多彩な臓器湿潤を認めたMantle cell lymphoma." 臨床血液. 38. 520-525 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taniguchi,Toshiyasu: "Cyclin D1 overexpression detected by a simple competitive reverse transcription-polymerase chain reaction assay for lymphoid malignancies." Japanese Journal of Cancer Research. 89. 159-166 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uchimaru,Kaoru: "Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway." Leukemia Research. 22. 413-420 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida,Fumihiro: "Hairy cell leukemia with translocation (11 ; 20)(q13 ; q11) and overexpression of cyclin D1." Leukemia Research. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taniguchi,Taniguchi: "Expression of p21Cip1/Waf1/Sdi1 and p27Kip1 cyclin-dependent kinase inhibitors during human hematopoiesis." Blood. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orii K,Kobayashi H,Ueno M,Ishida F,Saitoh H,Hata S,Aoki K,Narita A,Shimodaira S,Kitano K,Uchimaru K,Motokura T.: "Mantle cell lymphoma with multiple extranodal involvement." Japanese Joumal of Clinical Hematology. 38-6. 520-525 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taniguchi T,Fujita A,Takahashi S,Uchimaru K,Yoshikawa M,Asano S,Fujita T,Motokura T.: "Cyclin D1 overexpression detected by a simple competitive reverse transcription-polymerase chain reaction assay lymphoid malignancies." Japanese Joumal of Cancer Research. 89. 159-166 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uchimaru K,Taniguchi T,Yoshikawa M,Fujinuma H,Fujita T,Motokura: "Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway" Leukemia Research. 22. 413-420 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida F,Kitano K,Ichikawa N,Ito T,Kohara Y,Taniguchi T,Motokura T,Kiyosawa K.: "Hairy cell leukemia with translocation (11 ; 20)(q13 ; q11)and overexpression of cyclin D1." Leukemia Research. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taniguchi T,Endo H,Chikatsu N,Uchimaru K,Asano S,Fujita T,Nakahata T,Motokura T.: "Expression of p21Cip1/Waf1/Sdi1 and p27Kip1 cyclin-dependent kinase inhibitors during human hematopoiesis." Blood. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida,F.: "Hairy cell leukemia with translocation (11;20)(q13;q11) and overexpression of cyclin D1" Leukemia Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniguchi,F.: "Expression of p21 Cipl/Waf1/Sdi1 and p27Kip1 cyclin-dependent kinase inhibitors during human hematopoiecic" Blood. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 折井 幸司: "多彩な臓器浸潤を認めたMantle cell lymphoma." 臨床血液. 38. 520-525 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toshiyasu Taniguchi: "Cyclin D1 overexpression detected by a simple competitive reverse transcription-polymerase chain reaction assay for lymphoid malignancies." Japanese Journal of Cancer Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaoru Uchimaru: "Growth arrest associated with 12-0-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway." Leukemia Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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