Sj. Kim et al., NERVE GROWTH-FACTOR INDUCES TRANSCRIPTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 THROUGH A SPECIFIC PROMOTER ELEMENT IN PC12 CELLS, The Journal of biological chemistry, 269(5), 1994, pp. 3739-3744
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.