ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
批准号:
6633659
负责人:
Bihui Hilda Ye
金额:
$34.35万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-05-01 至 2005-04-30
中文摘要
描述:(改编自研究者摘要)攻击性非
何杰金氏B细胞淋巴瘤经常携带染色体易位,
原癌基因BCL-6位点。易位通过以下途径解除BCL-6表达的调节
启动子替换,导致野生型的组成性高水平
淋巴瘤B细胞中BCL-6蛋白。在正常的B细胞中,BCL-6蛋白是
只在中央舞台表现出来。BCL-6是一种含锌指蛋白,
转录抑制子小鼠基因敲除研究表明,
BCL-6在免疫系统中的调节功能。不过,
已知其表达在B和非B中通常是如何调节的
细胞此外,BCL-6表达异常的机制
对淋巴瘤发生的影响尚不清楚。第一个具体目标将
试图描述一个负性的自身调节机制,控制BCL-6
转录。实验的目的是首先确定它的存在
在具有野生型BCL-6基因的B细胞中。它在肿瘤B细胞中的完整性
然后研究基因改变的BCL-6基因。第二个目标,我们将
验证我们的假设,即BCL-6蛋白的持续表达是必要的,
用于维持淋巴瘤细胞系的致瘤性。我们将尝试
BCL-6蛋白的活性下调,
反义或显性失活BCL-6突变体(敲低方法)。
淋巴瘤细胞的细胞表型的相应变化将是
研究了我们的初步数据表明,BCL-6在预防
细胞凋亡,确定BCL-6和细胞凋亡调节因子之间的联系将是一个新的研究方向。
要务第三个目标是寻找BCL-6基因
基于这种击倒的方法。cDNA RDA和cDNA的组合
将使用微阵列技术。最后一个具体目标是建立
BCL-6在体内淋巴瘤发生中的致病作用
使用cre-lox系统的BCL-6转基因小鼠。待分析的表型
包括生发中心进入功能、B细胞增殖和肿瘤发生。
英文摘要
DESCRIPTION: (Adapted from the investigator's abstract) Aggressive non
Hodgkin's B-cell lymphomas often carry chromosomal translocations in the
proto-oncogene BCL-6 locus. Translocations deregulate BCL-6 expression via
promoter substitution, leading to constitutive high levels of the wild type
BCL-6 protein in lymphoma B cells. In normal B cells, the BCL-6 protein is
expressed only at the germinal center stage. BCL-6 is a zinc finger-containing
transcription repressor. Knock out studies in mice have suggested important
regulatory functions for BCL-6 in the immune system. Still, very little is
known about how its expression is normally regulated in B as well as in non-B
cells. In addition, the mechanism by which abnormal BCL-6 expression
contributes to lymphomagenesis is still unclear. The first specific aim will
attempt to characterize a negative autoregulatory mechanism governing BCL-6
transcription. Experiments are designed to first firmly establish its existence
in B cells with a wild type BCL-6 gene. Its integrity in tumor B cells with
genetically altered BCL-6 gene will then studied. In the second aim, we will
test our hypothesis that continued expression of the BCL-6 protein is essential
for maintaining the tumorigenicity of lymphoma cell lines. We will attempt to
downregulate the activity of BCL-6 protein by expression of either the
antisense or dominant negative BCL-6 mutants (knock down approach).
Corresponding changes in the cellular phenotype of lymphoma cells will be
studied. As our preliminary data suggests a role of BCL-6 in preventing
apoptosis, identifying a link between BCL-6 and apoptosis regulators will be a
priority. In the third aim, effort will be made to search for BCL-6 genes genes
based upon this knock down approach. A combination of cDNA RDA and the cDNA
microarray techniques will be used. The last specific aim is to establish the
causative role of BCL-6 in lymphomagenesis in vivo by generating conditional
BCL-6 transgenic mice using the cre-lox system. Phenotypes to be analyzed
include germinal center enter function, B cell proliferation and tumorigenesis.
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Epigenetic Alterations and Targeted Therapies in North American ATLL
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批准号:10660553
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项目类别:
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资助金额:$55.24万
-
财政年份:2023
-
负责人:Bihui Hilda Ye
-
依托单位:
ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
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批准号:6377787
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项目类别:
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资助金额:$32.47万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
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批准号:6742486
-
项目类别:
-
资助金额:$35.38万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
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依托单位:
Role of the BCL 6 Proto Oncogene in B Cell Lymphomas
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批准号:7240556
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项目类别:
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资助金额:$34.42万
-
财政年份:2000
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负责人:Bihui Hilda Ye
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依托单位:
ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
-
批准号:6087115
-
项目类别:
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资助金额:$31.71万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
Role of the BCL 6 Proto Oncogene in B Cell Lymphomas
-
批准号:7767766
-
项目类别:
-
资助金额:$36.5万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
ROLE OF THE BCL 6 PROTO ONCOGENE IN B CELL LYMPHOMAS
-
批准号:6514421
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项目类别:
-
资助金额:$33.36万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
Role of the BCL 6 Proto Oncogene in B Cell Lymphomas
-
批准号:7388287
-
项目类别:
-
资助金额:$34.75万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
Role of the BCL 6 Proto Oncogene in B Cell Lymphomas
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批准号:7095350
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项目类别:
-
资助金额:$34.41万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
Role of the BCL 6 Proto Oncogene in B Cell Lymphomas
-
批准号:7572953
-
项目类别:
-
资助金额:$35.79万
-
财政年份:2000
-
负责人:Bihui Hilda Ye
-
依托单位:
海外基金