BASIS OF PAX3-FKHR ONCOGENESIS IN RHABDOMYOSARCOMA

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。

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.