| Project/Area Number |
07557329
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
HAYASHI Norio Tohoku University, School of Medicine, Professor, 医学部, 教授 (00004606)
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| Co-Investigator(Kenkyū-buntansha) |
FURUYAMA Kazumichi Tohoku University, School of Medicine, Assistant Professor, 医学部, 助手 (80280874)
MINEGISHI Naoko University of Tsukuba, Institute of Baseic Medical Sciences, Associate Professor, 基礎医学系, 講師 (40271895)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | GATA-2 / transcription factor / enhancer / promoter / leukemia cells / hematopoiesis / transgenic mouse / GATA-1因子 / GATA-2因子 / 血球分化 / 白血病 / プロモーター / 造血細胞 / トロンボポエチン / MLP / M-TAT細胞 / GATA因子 / 造血前駆細胞 / 病型診断 |
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| Research Abstract |
The expression of GATA-2 is related to proliferative versus differentiated capability of hematopoietic progenitor cells, and suppression of GATA-2 seems to be essential for hematopoietic differentiation. Therefore, elucidation of the mechanisms controlling GATA-2 expression may offer insight into the earliest aspects of hematopoietic cellular differentiation and may help clarify the mechanisms underlying leukemogenesis, In the present study, we analyzed GATA expression profiles in leukemia cells and also analyzed the regulatory mechanism of GATA-2 gene.
(1) The expression of GATA-2 is closely linked with that of the CD34 antigen in established leukemia cell lines. To ascertain whether the expression profiles of GATA factors are preserved or changed in maligant counterparts of hematopoietic cells, we analyzed primary leukemic blasts from leukemic children, and found a correlation between tumor and respective normal cells in terms of the GATA factors. Namely, in the majority of myelogenou
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s leukemia cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from lymphoblastic leukemia (ALL) patients. GATA-3 mRNA was exressed in all T-ALL cases, but not in any precursor B-ALL.Therefore, exprression analysis of GATA factors may provide a useful tool to determine the lineage commitment of unclassified leukemia.
(2) We isolated and characterized the murine GATA-2 gene, and found that GATA-2 expression is regulated by two distinct promoters. One (IG promoter) is used in general in the tissues and cell lines that express GATA-2. The other promoter (IS promoter) regulates the expression of GATA-2 specifically in hematopoietic cells.
(3) We examined the regulatory activity of the mouse GATA-2 genomic locus in vivo using transgenic mice. Trans genes containing about 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of BETA-galactosidase reporter gene specifically to the para-aortic splanchnopleula, aorta-ganad-mesonephros region and in the neural tissues, In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenaous expression profiles of GATA-2 in these tissues. Less
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