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2005 Fiscal Year Final Research Report Summary

Functional analysis of Blimp-1

Research Project

Project/Area Number 16590924
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

HANGAISHI Akira  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20344450)

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)
Project Period (FY) 2004 – 2005
KeywordsBlimp-1 / cell cycle
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.

  • Research Products

    (8 results)

All 2006 2005

All Journal Article (8 results)

  • [Journal Article] Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization.2006

    • Author(s)
      Hosoya N
    • Journal Title

      Genes Chromosomes Cancer 45・5

      Pages: 482-494.

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization.2006

    • Author(s)
      Hosoya N, Sanada M, Nannya Y, Nakazaki K, Wang L, Hangaishi A, Kurokawa M, Chiba S, Ogawa S.
    • Journal Title

      Genes Chromosomes Cancer. 45(5)

      Pages: 482-494

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia : analysis in adults and children.2005

    • Author(s)
      Lee SY
    • Journal Title

      Leukemia 19・10

      Pages: 1841-1843

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays.2005

    • Author(s)
      Nannya Y
    • Journal Title

      Cancer Research 65・14

      Pages: 6071-6079.

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation.2005

    • Author(s)
      Hosoya N
    • Journal Title

      Genes Chromosomes Cancer 42・3

      Pages: 269-279

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia : analysis in adults and children.2005

    • Author(s)
      Lee SY, Kumano K, Masuda S, Hangaishi A, Takita J, Nakazaki K, Kurokawa M, Hayashi Y, Ogawa S, Chiba S.
    • Journal Title

      Leukemia 19(10)

      Pages: 1841-1843

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays.2005

    • Author(s)
      Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, Kurokawa M, Chiba S, Bailey DK, Kennedy GC, Ogawa S.
    • Journal Title

      Cancer Res. 65(14)

      Pages: 6071-6079

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation.2005

    • Author(s)
      Hosoya N, Qiao Y, Hangaishi A, Wang L, Nannya Y, Sanada M, Kurokawa M, Chiba S, Hirai H, Ogawa S.
    • Journal Title

      Genes Chromosomes Cancer 42(3)

      Pages: 269-279

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

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Published: 2007-12-13  

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