Expression of the repressor element-1 silencing transcription factor (REST) is influenced by insulin-like growth factor-I in differentiating human neuroblastoma cells.

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.

• Authors: Rosanna Di Toro, Monica Baiula, Santi Spampinato
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 21 Issue 1 Pg. 46-58 (Jan 2005) ISSN: 0953-816X [Print] France
• PMID: 15654842 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Culture Media, Serum-Free
• GAP-43 Protein
• Oligodeoxyribonucleotides, Antisense
• RE1-silencing transcription factor
• RNA, Messenger
• Repressor Proteins
• Synapsins
• Transcription Factors
• Tubulin
• Tritium
• Insulin-Like Growth Factor I
• Mitogen-Activated Protein Kinases
• Thymidine

Topics

• Antibodies (pharmacology)
• Blotting, Western (methods)
• Cell Differentiation (drug effects, physiology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Culture Media, Serum-Free (pharmacology)
• Drug Interactions
• Electrophoretic Mobility Shift Assay (methods)
• Enzyme Activation (drug effects)
• GAP-43 Protein (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Immunohistochemistry (methods)
• Insulin-Like Growth Factor I (pharmacology)
• Mitogen-Activated Protein Kinases (metabolism)
• Neurites (drug effects)
• Neuroblastoma
• Oligodeoxyribonucleotides, Antisense (pharmacology)
• RNA, Messenger (biosynthesis)
• Repressor Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Synapsins (metabolism)
• Thymidine (pharmacokinetics)
• Time Factors
• Transcription Factors (genetics, metabolism)
• Tritium (pharmacokinetics)
• Tubulin (metabolism)