BASIS OF PAX3-FKHR ONCOGENESIS IN RHABDOMYOSARCOMA

横纹肌肉瘤中 PAX3-FKHR 致癌的基础

• 批准号: 2733361
• 负责人: CHIAYENG WANG
• 金额: $ 8.73万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733361
• 关键词: athymic mouse; carcinogenesis; chemical binding; growth factor receptors; molecular oncology; molecular site; platelet derived growth factor; protein sequence; receptor expression; rhabdomyosarcoma; transcription factor

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.

描述：（改编自摘要。）长期目标 拟议的研究旨在了解 PAX3-FKHR 在肺泡中的作用 横纹肌肉瘤 (ARMS)，一种胎儿骨骼来源的肿瘤，最常见 常见于儿童。 PAX3-FKHR 是 t(2;13) ARMS 相关的产物 染色体易位。 该嵌合转录因子包含 PAX3 DNA 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）。 这是第一个 受 PAX3-FKHR 特别影响的细胞靶基因的示例 而不是 PAX3。 第一个具体目标是描绘 PAX3-FKHR 响应 PDGFaR 基因侧翼的元件。 第二个目标是绘制蛋白质图谱 PAX3-FKHR 中的基序使其能够激活 PDGFaR 基因。 这 第三个目标是检查 PDGFaR 功能如何促进 ARMS 肿瘤细胞 生长。 由于 PDGF 是一种有效的有丝分裂生长因子，异常表达 其受体的功能可能在细胞转化中发挥至关重要的作用。