INDUCTION OF TRKB BY RETINOIC ACID MEDIATES BIOLOGIC RESPONSIVENESS TO BDNF AND DIFFERENTIATION OF HUMAN NEUROBLASTOMA-CELLS

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 t he neurotrophins BDNF, NT-3, and NT-415. BDNF addition to RA-treated S H-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 express ion of TrkB and differentiation in the absence of added BDNF. Finally, in 15N neuroblastoma cells, which express BDNF mRNA but do not differ entiate in response to RA, RA induced only a truncated form of TrkB. 1 5N cells transfected with full-length TrkB differentiated in the absen ce of RA. These results indicate that RA induces the neuronal differen tiation of neuroblastoma cells by modulating the expression of neurotr ophin receptors.