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Expression of the repressor element-1 silencing transcription factor (REST) is influenced by insulin-like growth factor-I in differentiating human neuroblastoma cells
- Source :
- European Journal of Neuroscience. 21:46-58
- Publication Year :
- 2005
- Publisher :
- Wiley, 2005.
-
Abstract
- The repressor element-1 (RE-1) silencing transcription factor (REST) interacts with an RE-1 cis element and represses the transcription of neuron-specific genes in neuronal progenitors but is down-regulated in post-mitotic neurons. We report that REST expression is modified, in a time-dependent manner, in SH-SY5Y neuroblastoma cells exposed to insulin-like growth factor I (IGF-I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF-I for 2 days and then declines in 5-day-treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF-I, we employed an antisense oligonucleotide (AS-ODN) complementary to REST mRNA. In AS-ODN-treated cells, the effects elicited by IGF-I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and betaIII-tubulin gene promoters contain an RE-1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF-I for 5 days and further elevated by AS-ODN treatment. A parallel increase of growth cone-associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF-I and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.
- Subjects :
- NEURON-RESTRICTIVE SILENCER FACTOR
Time Factors
Neurite
medicine.medical_treatment
Blotting, Western
Repressor
Electrophoretic Mobility Shift Assay
Biology
Tritium
Antibodies
Culture Media, Serum-Free
Oligodeoxyribonucleotides, Antisense
Differentiating Neuroblastoma
GAP-43 Protein
Tubulin
Cell Line, Tumor
Neurites
medicine
Humans
Drug Interactions
RNA, Messenger
TRANSCRIPTION FACTOR
Insulin-Like Growth Factor I
Transcription factor
Cell Proliferation
Reverse Transcriptase Polymerase Chain Reaction
General Neuroscience
Growth factor
Neurogenesis
Cell Differentiation
Promoter
Synapsins
Immunohistochemistry
Molecular biology
Enzyme Activation
Repressor Proteins
DIFFERENTIATION
Gene Expression Regulation
NEUROBLASTOMA
Mitogen-Activated Protein Kinases
Neural development
INSULIN-LIKE GROWTH FACTOR-1
Thymidine
Transcription Factors
Subjects
Details
- ISSN :
- 14609568 and 0953816X
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- European Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....88320633d79d22b2178b5e4cb89667b9