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首页> 外文期刊>Molecular and Cellular Biology >Tumor cell complementation groups based on myogenic potential: evidence for inactivation of loci required for basic helix-loop-helix protein activity.
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Tumor cell complementation groups based on myogenic potential: evidence for inactivation of loci required for basic helix-loop-helix protein activity.

机译:基于成肌潜能的肿瘤细胞互补群:基本螺旋-环-螺旋蛋白活性所需基因座失活的证据。

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摘要

Basic helix-loop-helix (bHLH) proteins mediate terminal differentiation in many lineages. By using the bHLH protein MyoD, which can dominantly activate the myogenic differentiation program in numerous cell types, we demonstrated that recessive defects in bHLH protein function are present in human tumor lines. In contrast to prior work with primary cell cultures, MyoD did not activate the myogenic program in six of the eight tumor lines we tested. Cell fusions between the MyoD-defective lines and fibroblasts restored MyoD activity, indicating that the deficiency of a gene or factor prevents bHLH protein function in the tumor lines. Fusions between certain pairings of the MyoD-defective lines also restored MyoD activity, allowing the tumor lines to be assigned to complementation groups on the basis of their ability to execute the myogenic program and indicating that multiple mechanisms exist for abrogation of bHLH protein activity. These groups provide a basis for identifying genes critical for bHLH-mediated differentiation and tumor progression by using genetic complementation.
机译:基本的螺旋-环-螺旋(bHLH)蛋白介导许多谱系的终末分化。通过使用bHLH蛋白MyoD(可以在许多细胞类型中显性激活肌原性分化程序),我们证明了bHLH蛋白功能的隐性缺陷存在于人类肿瘤细胞系中。与原代细胞培养的先前工作相反,MyoD在我们测试的八个肿瘤系中的六个中并未激活肌源性程序。 MyoD缺陷型细胞与成纤维细胞之间的细胞融合恢复了MyoD活性,表明基因或因子的缺乏阻止了肿瘤细胞中bHLH蛋白的功能。某些配对的MyoD缺陷型细胞对之间的融合也恢复了MyoD活性,使肿瘤细胞可以根据其执行肌原性程序的能力分配给互补组,并表明存在多种消除bHLH蛋白活性的机制。这些小组为通过遗传互补鉴定对bHLH介导的分化和肿瘤进展至关重要的基因提供了基础。

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