Selective transcription and cellular proliferation induced by PDGF require histone deacetylase activity

Histone deacetylases (HDACs) are key regulatory enzymes involved in the control of gene expression and their inhibition by specific drugs has been widely correlated to cell cycle arrest, terminal differentiation, and apoptosis. Here, we investigated whether HDAC activity was required for PDGF-depend...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-05, Vol.343 (2), p.544-554
Main Authors: Catania, Annunziata, Iavarone, Carlo, Carlomagno, Stella M., Chiariello, Mario
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
DRUGS
Enzyme Activation - drug effects
ENZYMES
FIBROBLASTS
Histone deacetylase inhibitors
Histone Deacetylases - metabolism
IN VITRO
IN VIVO
INHIBITION
Mice
NIH 3T3 Cells
ONCOGENES
PHOSPHORYLATION
Platelet-Derived Growth Factor - administration & dosage
RECEPTORS
STAT activation
STAT Transcription Factors - metabolism
TRANSCRIPTION
Transcriptional Activation - drug effects
TRANSLOCATION
TYROSINE
Tyrosine kinase receptors
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Summary:Histone deacetylases (HDACs) are key regulatory enzymes involved in the control of gene expression and their inhibition by specific drugs has been widely correlated to cell cycle arrest, terminal differentiation, and apoptosis. Here, we investigated whether HDAC activity was required for PDGF-dependent signal transduction and cellular proliferation. Exposure of PDGF-stimulated NIH3T3 fibroblasts to the HDAC inhibitor trichostatin A (TSA) potently repressed the expression of a group of genes correlated to PDGF-dependent cellular growth and pro-survival activity. Moreover, we show that TSA interfered with STAT3-dependent transcriptional activity induced by PDGF. Still, neither phosphorylation nor nuclear translocation and DNA-binding in vitro and in vivo of STAT3 were affected by using TSA to interfere with PDGF stimulation. Finally, TSA treatment resulted in the suppression of PDGF-dependent cellular proliferation without affecting cellular survival of NIH3T3 cells. Our data indicate that inhibition of HDAC activity antagonizes the mitogenic effect of PDGF, suggesting that these drugs may specifically act on the expression of STAT-dependent, PDGF-responsive genes.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.03.013