Kim S J, Park K, Rudkin B B, Dey B R, Sporn M B, Roberts A B
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1994 Feb 4;269(5):3739-44.
Nerve growth factor (NGF) stimulates the differentiation of PC12 pheochromocytoma cells to those resembling sympathetic neurons. We have investigated whether NGF regulates transforming growth factor (TGF)-beta gene expression and protein secretion in PC12 cells. These cells constitutively express TGF-beta 1 mRNA, whereas TGF-beta 2 and -beta 3 mRNAs are expressed at very low levels. TGF-beta 1 gene expression was stimulated greater than 10-fold when PC12 cells were treated with NGF. Sequences between -119 and -98 in the TGF-beta 1 promoter, homologous to an Egr-1 binding site, were shown to be important for both basal and NGF-induced promoter activity. We also found that a factor(s) present in nuclear extracts from PC12 cells interacted with the sequences between -119 and -98 and that expression of this factor was induced by NGF treatment. Moreover, specific binding to TGF-beta 1 promoter fragments between -119 and -98 was seen using the bacterially expressed transcription factor Egr-1. These results indicate that activation of TGF-beta 1 expression is one of the cellular responses of PC12 cells to NGF and suggest that TGF-beta may play a role in the differentiation of sympathetic neurons.
神经生长因子（NGF）刺激嗜铬细胞瘤PC12细胞分化为类似交感神经元的细胞。我们研究了NGF是否调节PC12细胞中转化生长因子（TGF）-β基因表达和蛋白质分泌。这些细胞组成性表达TGF-β1 mRNA，而TGF-β2和-β3 mRNA的表达水平非常低。当用NGF处理PC12细胞时，TGF-β1基因表达被刺激增加超过10倍。TGF-β1启动子中与Egr-1结合位点同源的-119至-98之间的序列对于基础启动子活性和NGF诱导的启动子活性均很重要。我们还发现PC12细胞核提取物中存在的一种因子与-119至-98之间的序列相互作用，并且该因子的表达由NGF处理诱导。此外，使用细菌表达的转录因子Egr-1可观察到与-119至-98之间的TGF-β1启动子片段的特异性结合。这些结果表明TGF-β1表达的激活是PC12细胞对NGF的细胞反应之一，并提示TGF-β可能在交感神经元的分化中起作用。
