| Project/Area Number |
16590924
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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 |
HANGAISHI Akira The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20344450)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Mineo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80312320)
CHIBA Shigeru The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助教授 (60212049)
OGAWA Seishi The University of Tokyo, Faculty of Medicine, visiting Assistant Professor, 医学部附属病院, 客員助教授 (60292900)
KANDA Yoshinibu The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (30334379)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Blimp-1 / cell cycle / ノックアウトマウス |
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| Research Abstract |
Blimp-1 is a transcriptional repressor and essential for B cell maturation to immunoglobulin producing cells. Recently, we revealed that Blimp-1 gene is mutated in a part of lymphoid malignancies. This result indicates that Blimp-1 may act as a tumor suppressor. To explore the physiological role of Blimp-1, especially with relation to tumorigenesis, we disrupted the Blimp-1 gene of mice, generated Blimp-1 deficient mice. Blimp-1^<-/-> mice were not born. Blimp-1^<+/-> mice were born and grew to adulthood. No pathological abnormality was observed. To elucidate the function of Blimp-1 in adulthood, we also constructed conditional knockout mice of the Blimp-1 gene. We found splenomegaly and lymphadenopathy in Blimp-1 defected mice. Immunostaining and flow cytometry analyses revealed that polyclonal T cells in spleen and lymph nodes increased.
At the same time, we analyzed the function of Blimp-1 in vitro. Ectopic expression of Blimp-1 in tumor cell lines leads to growth arrest. In this reason, we have been focusing on investigating its impact on cell cycle control. Ectopic expression of Blimp-1 in cell lines leads to cell cycle arrest, and these cells showed considerable G1 and G2 accumulation by FACS analysis. Expression analyses by GeneChip revealed that expression of Blimp-1 in these cells led to a prominent elevation of several genes expression. To further explore how Blimp-1 associates with these regulators on the cell cycle control, we employed siRNA to eliminate the endogenous expressions of these regulators separately. Blimp-1 induced G1 and G2 arrest is dependent on wild type Rb and p53.
These results suggest that Blimp-1 plays a pivotal role in cell cycle control and the suppression of tumor formation.
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