The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture
The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture
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DOI：
10.1073/pnas.93.18.9805
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Vogt, PK
中科院分区：
文献类型：
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作者：
Scheidler, S;Fredericks, WJ;Vogt, PK
小儿肺泡横纹肌肉瘤的特点是染色体易位，融合了部分PAX3和FKHR基因。PAX3编码控制发育程序的转录调节因子，FKHR编码叉翼螺旋蛋白，也是一种可能的转录因子。PAX3-FKHR融合产物保留了PAX3蛋白的DNA结合域和FKHR蛋白的推定激活域。PAX3-FKHR蛋白已被证明具有转录激活因子的功能。利用RCAS逆转录病毒载体，将PAX3-FKHR基因导入鸡胚成纤维细胞。PAX3-FKHR蛋白在这些细胞中的表达导致转化：细胞变大，排列紧密，呈多层生长，并获得不依赖锚定生长的能力。这种体外细胞转化将有助于研究pax3 - fkhr诱导肿瘤发生的机制。
Pediatric alveolar rhabdomyosarcoma is characterized by a chromosomal translocation that fuses parts of the PAX3 and FKHR genes. PAX3 codes for a transcriptional regulator that controls developmental programs, and FKHR codes for a forkhead-winged helix protein, also a likely transcription factor. The PAX3-FKHR fusion product retains the DNA binding domains of the PAX3 protein and the putative activator domain of the FKHR protein. The PAX3-FKHR protein has been shown to function as a transcriptional activator. Using the RCAS retroviral vector, we have introduced the PAX3-FKHR gene into chicken embryo fibroblasts. Expression of the PAX3-FKHR protein in these cells leads to transformation: the cells become enlarged, grow tightly packed and in multiple layers, and acquire the ability for anchorage-independent growth. This cellular transformation in vitro will facilitate studies on the mechanism of PAX3-FKHR-induced oncogenesis.