Nerve growth factor induces transcription of transforming growth factor-beta 1 through a specific promoter element in PC12 cells.

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.