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BASIS OF PAX3-FKHR ONCOGENESIS IN RHABDOMYOSARCOMA

BASIS OF PAX3-FKHR ONCOGENESIS IN RHABDOMYOSARCOMA
横纹肌肉瘤中 PAX3-FKHR 致癌的基础
批准号:
2896046
负责人:
CHIAYENG WANG
金额:
$11.18万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-07-15 至 2002-06-30

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中文摘要
翻译
描述:(改编自摘要。)世界银行的长期目标 拟议的研究是为了了解PAX3-FKHR在肺泡中的作用 横纹肌肉瘤(ARMS)是一种起源于胎儿骨骼的肿瘤,最常见的 在儿童中很常见。Pax3-FKHR是t(2;13)ARM相关的产物 染色体易位。该嵌合转录因子含有 Pax3DNA结合域和(更强的)FKHR反式激活域。 初步研究表明,PAX3-FKHR异常激活该基因 血小板衍生生长因子α受体(PDGFaR)。这是第一次 一例受PAX3-FKHR特异性影响的细胞靶基因 而不是PAX3。第一个具体目标是描绘PAX3-FKHR反应 位于PDGFaR基因两侧的元件。第二个目标是绘制蛋白质图谱 PAX3-FKHR中的基序(S)使其能够激活PDGFaR基因。这个 第三个目的是研究PDGFaR功能对ARM肿瘤细胞的作用 成长。由于PDGF是一种强有力的有丝分裂生长因子,因此异常表达 其受体的表达可能在细胞转化中起关键作用。
英文摘要
DESCRIPTION: (Adapted from the abstract.) The long range goal of the proposed research is to understand the role of PAX3-FKHR in alveolar rhabdomyosarcoma (ARMS), a tumor of fetal skeletal origin that is most common in children. PAX3-FKHR is a product of t(2;13) ARMS-associated chromosomal translocations. This chimeric transcription factor contains the PAX3 DNA binding domain and the (stronger) FKHR transactivation domain. Preliminary studies show that PAX3-FKHR aberantly activates the gene for the platelet derived growth factor alpha receptor (PDGFaR). This is the first example of a cellular target gene that is specifically affected by PAX3-FKHR and not PAX3. The first specific aim is to delineate the PAX3-FKHR response element that flanks the PDGFaR gene. The second aim is to map the protein motif(s) in PAX3-FKHR that enables it to activate the PDGFaR gene. The third aim is to examine how PDGFaR function contributes to ARMS tumor cell growth. Since PDGF is a potent mitotic growth factor, aberrant expression of its receptor is likely to play a crucial role in cell transformation.
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Basis of PAX3-FKHR oncogenesis in rhabdomyosarcoma
Basis of PAX3-FKHR oncogenesis in rhabdomyosarcoma
Basis of PAX3-FKHR oncogenesis in rhabdomyosarcoma
Basis of PAX3-FKHR oncogenesis in rhabdomyosarcoma
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