title: Nerve growth factor induces transcription of transforming growth factor-beta 1 through a specific promoter element in PC12 cells.
abstract: 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.
authors.affiliation: Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: B B
authors.initials: BB
authors.lastname: Rudkin
authors.forename: B R
authors.initials: BR
authors.lastname: Dey
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
authors.forename: A B
authors.initials: AB
authors.lastname: Roberts
mesh_terms: D000310:Adrenal Gland Neoplasms; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007700:Kinetics; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides; D016716:PC12 Cells; D010673:Pheochromocytoma; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D015500:Chloramphenicol O-Acetyltransferase