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 pheoc hromocytoma cells to those resembling sympathetic neurons. We have inv estigated whether NGF regulates transforming growth factor (TGF)-beta gene expression and protein secretion in PC12 cells. These cells const itutively express TGF-beta1 mRNA, whereas TGF-beta2 and -beta3 mRNAs a re expressed at very low levels. TGF-beta1 gene expression was stimula ted greater than 10-fold when PC12 cells were treated with NGF. Sequen ces between -119 and -98 in the TGF-beta1 promoter, homologous to an E gr-1 binding site, were shown to be important for both basal and NGF-i nduced promoter activity. We also found that a factor(s) present in nu clear extracts from PC12 cells interacted with the sequences between - 119 and -98 and that expression of this factor was induced by NGF trea tment. Moreover, specific binding to TGF-beta1 promoter fragments betw een -119 and -98 was seen using the bacterially expressed transcriptio n factor Egr-1. These results indicate that activation of TGF-beta1 ex pression is one of the cellular responses of PC12 cells to NGF and sug gest that TGF-beta may play a role in the differentiation of sympathet ic neurons.