Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein
Transcriptional regulation of IGF-I receptor gene expression by the PAX3-FKHR oncoprotein
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DOI：
10.1054/ghir.2001.0244
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发表时间：
2001-10-01
影响因子：
1.4
通讯作者：
Werner, H.
中科院分区：
文献类型：
--
作者：
Ayalon, D.;Glaser, T.;Werner, H.
破坏转录因子分子结构的染色体易位是多种实体癌和造血系统癌的典型表现。腺泡状横纹肌肉瘤（Alveolar rhabdomyosarcoma，ARMS）是一种儿童软组织恶性肿瘤，其特征是复发性易位t（2;13）（q35;q14），该易位融合了Pax 3基因的5' DNA结合结构域编码序列和FKHR基因的3'序列。胰岛素样生长因子（IGF）系统在肌肉发育以及儿童肉瘤（包括ARMS）的病因学中起重要作用。在本研究中，研究了PAX 3-FKHR在转录水平对IGF-I受体（IGF-I-R）基因的潜在调控。PAX 3-FKHR能够在肉瘤衍生的细胞系中反式激活IGF-I-R启动子，而PAX 3与融合蛋白相比表现出降低的效力。此外，嵌合体的转染诱导内源性IGF-I-R蛋白水平的显著增加，表明IGF-I-R基因是PAX 3-FKHR癌基因的生理相关分子靶点。
Chromosomal translocations that disrupt the molecular organization of transcription factors are typical of a variety of solid and hematopoietic cancers. Alveolar rhabdomyosarcoma (ARMS), a paediatric soft tissue malignant tumour, is characterized by the recurrent translocation t(2;13)(q35;q14) that fuses the 5' DNA binding domain-encoding sequences of the Pax3 gene with the 3' sequences of the FKHR gene. The insulin-like growth factor (IGF) system has an important role in muscle development as well as in the aetiology of paediatric sarcomas, including ARMS. In the present study the potential regulation of the IGF-I receptor (IGF-I-R) gene by PAX3-FKHR at the transcriptional level was investigated. PAX3-FKHR was able to transactivate the IGF-I-R promoter in sarcoma-derived cell lines, whereas PAX3 exhibited a reduced potency in comparison to the fusion protein. Furthermore, transfection of the chimera induced a significant increase in the endogenous levels of IGF-I-R protein, suggesting that the IGF-I-R gene is a physiologically-relevant molecular target for the PAX3-FKHR oncogene.