1999 Fiscal Year Final Research Report Summary
Study for the mechanism of lymphocyte development by NF-E2 transcription factors and clinical analysis of NF-E2 gene.
| Project/Area Number |
10670700
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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 |
Pediatrics
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| Research Institution | HIROSAKI UNIVERSITY |
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Principal Investigator |
ITO Etsuro Hirosaki University Hospital, Pediortrics, Assistant Professor, 医学部・付属病院, 講師 (20168339)
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| Co-Investigator(Kenkyū-buntansha) |
TOKI Tsutomu Hirosaki University School of Medicine, Pediortics Instructor, 医学部, 助手 (50195731)
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| Project Period (FY) |
1998 – 1999
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| Keywords | B cell / Bach 2 / Transcription factor |
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| Research Abstract |
The transcription factors Bach1 and Bach2, members of the BTB-basic region leucine zipper (bZip) factor family, bind to a 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and the related Maf-recognition element (MARE) by forming homodimers or heterodimers with Maf-related transcription factors. Among human hematopoietic cell lines (12 myeloid cell lines and 16 lymphocytic cell lines), BACH2 is expressed abundantly only in some B-lymphocytic cell lines. RT-PCR analysis of hematopoietic cells revealed that BACH2 mRNA is expressed in primary B-cells. Enforced expression of BACH2 in a human Burkitt cell line, RAJI that does not express endogenous BACH2, resulted in marked reduction of clonogenic activity, indicating that BACH2 possesses an inhibitory effect on cell proliferation. By fluorescent in situ hybridization, the BACH2 gene was localized to chromosome 6q15. Because deletion of the long arm of chromosome 6 (6q) is one of the commonest chromosomal alterations in human B-cell lymphoma, we examined for the loss of heterozygosity (LOH) of the BACH2 gene in human B-cell non-Hodgkin's lymphomas (NHL). Among 25 informative cases, 5 (20%) showed LOH. To analyze the mutations of BACH2 gene in these lymphomas, we examine the structure of the BACH2 gene and determined the sequences of the all coding exons and the exon-intron boundaries. By direct sequence analysis, no mutations were detected in the 5 lymphoma samples with the LOH of BACH2 gene . These results indicate that BACH2 plays important roles in regulation of B cell proliferation, although it remains still elusive whether loss of BACH2 function is involved in B-cell tumorigenesis.
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[Publications] Sasaki S, Ito E, Toki T, Maekawa T, Kanezaki R, Umenai T, Muto A, Nagai H, Kinoshita T, Yamamoto M, Inazawa J, Taketo MM, Nakahata T, lgarashi K, and Yokoyama M.: "Cloning and expression of human B cell-specific transcription factor BACH2, mapped to chromosome 6ql5."Oncogene. in press.
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