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TrkA induces differentiation but not apoptosis in C6-2B glioma cells
- Source :
- Journal of neuroscience research. 64(6)
- Publication Year :
- 2001
-
Abstract
- Nerve growth factor (NGF) binds to the TrkA tyrosine kinase and the p75 neurotrophin receptors. Depending upon which receptor is activated, NGF can induce differentiation or apoptosis. C6-2B glioma cells express the p75 receptor, but NGF decreases their growth only when TrkA is introduced (C6trk). It is unclear, however, whether TrkA reduces C6-2B cell growth by apoptosis or differentiation. To examine which mechanisms account for the anti-proliferative effect of NGF in these cells, we first analyzed whether NGF causes apoptosis by flow cytometry, two-site immunoassay and in situ TUNEL. None of these methods indicated that C6trk undergo apoptosis. Additional apoptotic markers, such as Bcl-2, Bax, Bad, p53, caspase 3, and NF-κB were also used. C6trk cells exhibited lower levels of Bcl-2 compared with the parental C6 mock cells, but no changes in the levels of other apoptotic proteins. Moreover, NGF increased AP-1 binding activity in C6trk cells, suggesting that NGF may induce differentiation. We then examined whether TrkA changes the glioma phenotype. In C6trk cells, but not in C6mock cells, NGF enhanced the levels of neuron-specific enolase as well as the levels of A2B5 and 2′, 3′-cyclic nucleotide 3′-phosphodiesterase, markers for oligodendrocytes, without affecting the expression of other neuronal markers. Our data suggest that the antiproliferative properties of TrkA may rely on its ability to induce differentiation of C6 cells from undifferentiated glioma to oligodendrocytes. J. Neurosci. Res. 64:636–645, 2001. © 2001 Wiley-Liss, Inc.
- Subjects :
- Caspase 3
Apoptosis
Tropomyosin receptor kinase A
Receptor, Nerve Growth Factor
Cellular and Molecular Neuroscience
Proto-Oncogene Proteins
Nerve Growth Factor
In Situ Nick-End Labeling
Tumor Cells, Cultured
Low-affinity nerve growth factor receptor
Animals
Phosphorylation
Receptor, trkA
bcl-2-Associated X Protein
biology
Cell growth
Chemistry
NF-kappa B
Cell Differentiation
Glioma
Rats
Transcription Factor AP-1
Oligodendroglia
Nerve growth factor
nervous system
Proto-Oncogene Proteins c-bcl-2
Cancer research
biology.protein
Tumor Suppressor Protein p53
Tyrosine kinase
Cell Division
Neurotrophin
Subjects
Details
- ISSN :
- 03604012
- Volume :
- 64
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of neuroscience research
- Accession number :
- edsair.doi.dedup.....d8f141f829ebf9c66e3f3a5809f42582