| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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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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