Ciliary neurotrophic factor coordinately activates transcription of neuropeptide genes in a neuroblastoma cell line.
Differentiation factors have been identified that influence the phenotype of sympathetic neurons by altering expression of classical neurotransmitters and neuropeptides. Investigation of the molecular mechanisms through which such factors act would be facilitated by the availability of a neuronal cell line that responds to these factors in a fashion similar to sympathetic neurons. We have identified a human neuroblastoma cell line, NBFL, that responds to the differentiation factor ciliary neurotrophic factor (CNTF) by coordinately inducing multiple neuropeptide genes as do sympathetic neurons. Treatment of NBFL cells with CNTF increases vasoactive intestinal polypeptide (VIP), somatostatin, and calcitonin gene-related peptide (CGRP) mRNAs but does not change other neurotransmitter properties. The induction of VIP mRNA by CNTF in NBFL cells is dose dependent, rapid, sustained, and independent of new protein synthesis. Genomic 5' flanking sequences located within a 1.59-kilobase region of the human VIP gene and distinct from the previously defined cAMP-responsive element subserve transcriptional activation by CNTF. Further examination of NBFL cells should permit the elucidation of the molecular mechanisms by which CNTF and other differentiation factors coordinately activate neuropeptide gene transcription to influence neuronal differentiation. Similar mechanisms may mediate the effect of CNTF on neuronal survival.
Symes
A J
AJ
Department of Neurology, Massachusetts General Hospital, Boston 02114.
Rao
M S
MS
Lewis
S E
SE
Landis
S C
SC
Hyman
S E
SE
Fink
J S
JS
D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D020934:Ciliary Neurotrophic Factor; D015870:Gene Expression; D005786:Gene Expression Regulation; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide