Study for the mechanism of lymphocyte development by NF-E2 transcription factors and clinical analysis of NF-E2 gene.

NF-E2转录因子影响淋巴细胞发育的机制研究及NF-E2基因临床分析。

• 批准号: 10670700
• 负责人: ITO Etsuro
• 金额: $ 1.98万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670700/
• 关键词: B cell; Bach 2; Transcription factor; Nrf3; Bリンパ球

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.

转录因子Bach1和Bach2是btb -碱性区亮氨酸拉链（bZip）因子家族的成员，通过与maf相关转录因子形成同源二聚体或异源二聚体，与12- o -十四烷醇-13-乙酸酯（TPA）响应元件和相关的maf识别元件（MARE）结合。在人造血细胞系（12种骨髓细胞系和16种淋巴细胞系）中，BACH2仅在部分b淋巴细胞系中丰富表达。造血细胞RT-PCR分析显示BACH2 mRNA在原代b细胞中表达。在不表达内源性BACH2的人Burkitt细胞系RAJI中，强制表达BACH2导致克隆生成活性明显降低，表明BACH2对细胞增殖具有抑制作用。通过荧光原位杂交，BACH2基因定位在6q15染色体上。由于6号染色体长臂缺失（6q）是人类b细胞淋巴瘤中最常见的染色体改变之一，我们检测了人类b细胞非霍奇金淋巴瘤（NHL）中BACH2基因杂合性缺失（LOH）。在25例资料丰富的病例中，5例（20%）表现为LOH。为了分析BACH2基因在这些淋巴瘤中的突变，我们检测了BACH2基因的结构，并确定了所有编码外显子的序列和外显子-内含子边界。通过直接序列分析，5例携带BACH2基因LOH的淋巴瘤样本均未发现突变。这些结果表明BACH2在B细胞增殖调控中发挥重要作用，尽管BACH2功能缺失是否参与B细胞肿瘤发生尚不清楚。

项目成果

Toki T.: "Functional Characterization of the Two Alternative Promoters of Human p45 NF-E2 Gene"Experimental Hematology. (in press).

Toki T.：“人类 p45 NF-E2 基因的两个替代启动子的功能表征”实验血液学。

Kobayashi A, Ito E, Toki T, Kogame K, Takahashi S, lgarashi K.Hayashi N and Yamamoto M: "Molecular cloning and functional characterization of a new CNC family transcription factor Nrf3."J. Biol. Chem. 274. 6443-6452 (1999)

Kobayashi A、Ito E、Toki T、Kogame K、Takahashi S、lgarashi K.Hayashi N 和 Yamamoto M：“新 CNC 家族转录因子 Nrf3 的分子克隆和功能表征。”J。

Sasaki S et al.: "Cloning and expression of human B cell-specific Transcription factor BACH2, mapped to chromosome6q15"Oncogene. (in press).

Sasaki S 等人：“人类 B 细胞特异性转录因子 BACH2 的克隆和表达，映射到染色体 6q15”癌基因。

Toki T et al.: "Functional Characterization of the Two Alternative Promoters of Human p45 NF-E2 Gene"Experimental Hematology. (in press).

Toki T 等人：“人 p45 NF-E2 基因的两个替代启动子的功能表征”实验血液学。