TrkA induces differentiation but not apoptosis in C6-2B glioma cells

Beth Pflug, Anna Maria Colangelo, Carlo Tornatore, Italo Mocchetti

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)636-645
Number of pages10
JournalJournal of Neuroscience Research
Volume64
Issue number6
DOIs
StatePublished - Jun 15 2001
Externally publishedYes

Fingerprint

Glioma
Nerve Growth Factor
Apoptosis
Nerve Growth Factor Receptor
Oligodendroglia
Phosphopyruvate Hydratase
Cyclic Nucleotides
Transcription Factor AP-1
Phosphoric Diester Hydrolases
In Situ Nick-End Labeling
Growth
Immunoassay
Caspase 3
Protein-Tyrosine Kinases
Cell Differentiation
Flow Cytometry
Phenotype
Proteins

Keywords

  • Apoptosis
  • Bcl-2
  • NF-κB
  • NGF
  • p53
  • p75NTR

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

TrkA induces differentiation but not apoptosis in C6-2B glioma cells. / Pflug, Beth; Colangelo, Anna Maria; Tornatore, Carlo; Mocchetti, Italo.

In: Journal of Neuroscience Research, Vol. 64, No. 6, 15.06.2001, p. 636-645.

Research output: Contribution to journalArticle

Pflug, Beth ; Colangelo, Anna Maria ; Tornatore, Carlo ; Mocchetti, Italo. / TrkA induces differentiation but not apoptosis in C6-2B glioma cells. In: Journal of Neuroscience Research. 2001 ; Vol. 64, No. 6. pp. 636-645.
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