| Project/Area Number |
09671092
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHARA Tatsutoshi The University of Tokyo, Institute of Medical Science Professor, 医科学研究所, 教授 (20110744)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| 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)
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| Keywords | HEMATOPOIESIS / CELL CYCLE / CYCLIN / p16INK4a / p21CIP1 / p27KIP1 / MEGAKARYOCYTE / TUMORIGENESIS / p21WAF1 |
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| 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.
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