Induction of TrkB by retinoic acid mediates biologic responsiveness to BDNF and differentiation of human neuroblastoma cells. Eukaryotic Signal Transduction Group

Neuron. 1993 Aug;11(2):321-31. doi: 10.1016/0896-6273(93)90187-v.


Retinoic acid (RA) induces the neuronal differentiation of many human neuroblastoma cell lines. In this study, we show that RA treatment of neuroblastoma cells induces the expression of TrkB, the receptor for the neurotrophins BDNF, NT-3, and NT-4/5. BDNF addition to RA-treated SH-SY5Y neuroblastoma cells stimulated the tyrosine phosphorylation of TrkB and neuronal differentiation. RA treatment of KCNR neuroblastoma cells, which constitutively express BDNF mRNA, resulted in the expression of TrkB and differentiation in the absence of added BDNF. Finally, in 15N neuroblastoma cells, which express BDNF mRNA but do not differentiate in response to RA, RA induced only a truncated form of TrkB. 15N cells transfected with full-length TrkB differentiated in the absence of RA. These results indicate that RA induces the neuronal differentiation of neuroblastoma cells by modulating the expression of neurotrophin receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Differentiation / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Nerve Growth Factors / pharmacology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology*
  • Neuroblastoma / pathology*
  • Neurons / pathology
  • Peptide Fragments / metabolism
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptor, trkA
  • Receptors, Cell Surface / metabolism
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology
  • Tyrosine / metabolism


  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tyrosine
  • Tretinoin
  • Protein-Tyrosine Kinases
  • Receptor, trkA