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Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells
- Source :
- FEBS Letters. 579:615-620
- Publication Year :
- 2004
- Publisher :
- Wiley, 2004.
-
Abstract
- This study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, β-catenin, c-Jun, c-Myc and Id2) and upregulation of those implicated in the osteoblastic differentiation (p21/Waf1, osteopontin, osteocalcin, type I collagen, N-cadherins and alkaline phosphatase). Our study suggests that use of PARP inhibitors may induce a remodeling of chromatin with the reprogramming of gene expression and the activation of differentiation.
- Subjects :
- Blotting, Western
Biophysics
Hyperphosphorylation
Cell Cycle Proteins
Poly(ADP-ribose) Polymerase Inhibitors
Cell cycle
Retinoblastoma Protein
Biochemistry
PARP
Rb protein
Cyclin D1
Downregulation and upregulation
Structural Biology
Cell Line, Tumor
Gene expression
Genetics
Humans
Immunoprecipitation
Osteopontin
Enzyme Inhibitors
Phosphorylation
E2F
Molecular Biology
DNA Primers
Adenosine Diphosphate Ribose
Osteosarcoma
Base Sequence
biology
Reverse Transcriptase Polymerase Chain Reaction
G1 Phase
Cell Differentiation
Cell Biology
Flow Cytometry
3-AB
E2F Transcription Factors
Chromatin
DNA-Binding Proteins
Gene Expression Regulation
Differentiation
Benzamides
biology.protein
Cancer research
Transcription Factors
Subjects
Details
- ISSN :
- 00145793
- Volume :
- 579
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....974e02e8154da6a224c60a163b3b08c0