Effect of a tumour promoter on myogenesis
Effect of a tumour promoter on myogenesis
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肿瘤启动子对肌生成的影响
作者：
R. Cohen;M. Pacifici;N. Rubinstein;J. Biehl;H. Holtzer
病毒和化学致癌物改变正在进行的细胞合成程序的证据已经提出1，2。用温度敏感性劳斯肉瘤病毒转化的成软骨细胞和成黑素细胞分别停止合成成软骨细胞特有的硫酸化蛋白多糖和黑色素3。转移到非允许的温度，这些细胞重新启动成软骨细胞独特的硫酸化蛋白多糖和黑色素的合成。使用鸡生肌细胞也获得了类似的结果4，5。正常的假定成肌细胞进行有限数量的复制，产生有丝分裂后的单核成肌细胞。有丝分裂后成肌细胞开始合成肌肉特异性肌球蛋白重链和轻链，并融合成肌管6，7。相反，ts病毒转化的肌原细胞继续复制，不启动肌肉特异性肌球蛋白的合成，也不融合。在转换到非允许温度后24-48 h，许多转化的肌原性细胞不可逆地从细胞周期中退出，开始合成肌肉特异性肌球蛋白（未发表的数据）并融合。显然，当转化因子表达时，细胞不会退出细胞周期，并且由于被迫循环，不会终末分化。为了探讨从正常前体细胞产生终末分化细胞和从正常前体细胞产生恶性细胞的共同机制，我们研究了佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）对肌发生的影响。在纯化的佛波醇酯中，PMA作为促肿瘤剂和促分裂剂是最有效的8 -12。我们在这里报告说，PMA模仿劳氏肉瘤肿瘤剂对肌生成的一些影响。
EVIDENCE that viruses and chemical carcinogens alter the ongoing synthetic programme of cells has been presented1,2. Chondroblasts and melanoblasts transformed with a temperature-sensitive Rous sarcoma virus cease synthesising the chondroblast-unique sulphated proteoglycan and melanin, respectively3. Shifted to non-permissive temperature, these cells re-initiate the synthesis of the chondroblast-unique sulphated proteoglycan and melanin. Similar results have been obtained using chick myogenic cells4,5. Normal presumptive myoblasts undergo a limited number of replications, yielding postmitotic, mononucleated myoblasts. Postmitotic myoblasts initiate the synthesis of muscle-specific myosin heavy and light chains and fuse into myotubes6,7. In contrast, ts-viral transformed myogenic cells continue to replicate, do not initiate the synthesis of muscle-specific myosins and do not fuse. 24–48 h after shifting to non-permissive temperature, many transformed myogenic cells withdraw irreversibly from the cell cycle, initiate the synthesis of muscle-specific (unpublished data) myosins and fuse. Apparently when the transformation factor is expressed the cells do not withdraw from the cell cycle, and as a consequence of being forced to cycle, do not terminally differentiate. To probe the mechanisms that might be common to the generation of terminally differentiated cells from normal precursor cells, and to the generation of malignant cells from normal precursor cells, we studied the effects of phorbol-12-myristate-13-acetate (PMA) on myogenesis. Of the purified phorbol esters, PMA is the most potent as a tumour-promoting agent and as a mitogen8–12. We report here that PMA mimics some of the effects of the Rous sarcoma tumour agent on myogenesis.