Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells.
Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells.
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DOI：
10.1016/s0021-9258(17)38689-1
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发表时间：
1985-11
期刊：
影响因子：
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通讯作者：
M. Greenberg;L. Greene;E. Ziff
中科院分区：
文献类型：
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作者：
M. Greenberg;L. Greene;E. Ziff
神经生长因子（NGF）促进PC 12嗜铬细胞瘤细胞向神经元分化。我们在这里表明，在5分钟内，它的添加后，神经生长因子瞬时刺激c-fos原癌基因和肌动蛋白的转录超过100倍，在非同步化的PC 12细胞。c-myc和鸟氨酸脱羧酶转录也被瞬时激活，但更慢。相应的mRNA也被诱导。暴露于NGF两周不会导致这些和其他各种基因的转录发生显著变化;然而，在这些条件下，c-fos mRNA水平增加了数倍。神经元分化的PC 12细胞保留了快速转录反应的能力。从这样的细胞中去除NGF几个小时，然后再添加，导致c-fos和肌动蛋白转录的快速诱导。PC 12细胞中这些NGF促进的转录变化类似于先前在由血小板衍生生长因子刺激的静止成纤维细胞中观察到的那些（Greenberg，M.E.，和Ziff，E. B.（1984）Nature 311，433-438）。在PC 12细胞中的这种快速转录激活可能是神经元分化所必需的，但显然是不够的，因为还发现没有分化活性的各种试剂如表皮生长因子、胰岛素、二丁酰cAMP、佛波酯和升高的K+也诱导转录。这些结果表明，c-fos，c-myc，和肌动蛋白的诱导可能是一般的核反应的生长或分化因子在各种不同的细胞类型。
Nerve growth factor (NGF) promotes neuronal differentiation of PC12 pheochromocytoma cells. We show here that within 5 min after its addition, NGF transiently stimulates c-fos proto-oncogene and actin transcription by greater than 100-fold in nonsynchronized PC12 cells. c-myc and ornithine decarboxylase transcription are also transiently activated, but more slowly. The corresponding mRNAs are induced as well. Two weeks' exposure to NGF causes no significant changes in the transcription of these and a variety of other genes analyzed; however, c-fos mRNA levels are increased severalfold under these conditions. Neuronally differentiated PC12 cells retain the capacity for rapid transcriptional responses. Removal of NGF from such cells for several hours followed by its readdition results in rapid induction of c-fos and actin transcription. These NGF-promoted transcriptional changes in PC12 cells are similar to those previously observed in quiescent fibroblasts stimulated by platelet-derived growth factor (Greenberg, M.E., and Ziff, E.B. (1984) Nature 311, 433-438). This rapid transcriptional activation in PC12 cells could be necessary for neuronal differentiation, but is apparently not sufficient since diverse agents without differentiating activity such as epidermal growth factor, insulin, dibutyryl cAMP, phorbol ester, and elevated K+ were also found to induce transcription. These results suggest that c-fos, c-myc, and actin induction may be general nuclear responses to growth or differentiation factors in a variety of different cell types.