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

• Published in: The Journal of biological chemistry 1994-02, Vol.269 (5), p.3739-3744
• Main Authors: Kim, S J, Park, K, Rudkin, B B, Dey, B R, Sporn, M B, Roberts, A B
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms; Animals; Base Sequence; Binding Sites; Blotting, Northern; Cell Nucleus - metabolism; Chloramphenicol O-Acetyltransferase - biosynthesis; Chloramphenicol O-Acetyltransferase - metabolism; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; Gene Expression - drug effects; Kinetics; Molecular Sequence Data; Nerve Growth Factors - pharmacology; Oligodeoxyribonucleotides; PC12 Cells; Pheochromocytoma; Plasmids; Promoter Regions, Genetic - drug effects; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; RNA, Neoplasm - analysis; Transcription Factors - biosynthesis; Transcription Factors - metabolism; Transcription, Genetic - drug effects; Transfection; Transforming Growth Factor beta - biosynthesis; Zinc Fingers
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)41922-3

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.