Neuron
Volume 11, Issue 2, August 1993, Pages 321-331
Journal home page for Neuron

Article
Induction of TrkB by retinoic acid mediates biologic responsiveness to BDNF and differentiation of human neuroblastoma cells

https://doi.org/10.1016/0896-6273(93)90187-VGet rights and content

Abstract

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.

References (72)

  • F. Lamballe et al.

    trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3

    Cell

    (1991)
  • D.M. Loeb et al.

    The trk proto-oncogene rescues NGF responsiveness in mutant NGF-non responsiveness PC12 cell lines

    Cell

    (1991)
  • P.C. Maisonpierre et al.

    NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression

    Neuron

    (1990)
  • M. Maden et al.

    Cellular retinoic acid-binding protein and the role of retinoic acid in the development of the chick embryo

    Dev. Biol.

    (1989)
  • R.J. Scheibe et al.

    Retinoic acid regulates both expression of the nerve growth factor receptor and sensitivity to nerve growth factor

    J. Biol. Chem.

    (1992)
  • P. Tsoulfas et al.

    The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to NT-3 in PC12 cells

    Neuron

    (1993)
  • L. Wuarin et al.

    Differential susceptibilities of spinal cord neurons to retinoic acid-induced survival and differentiation

    Dev. Biol.

    (1991)
  • L. Wuarin et al.

    Retinoids increase neuronal survival and astrocyte differentiation in rat spinal cord

    Intl. J. Dev. Neurosci.

    (1990)
  • E. Abemayor et al.

    Human neuroblastoma cell lines as models for the in vitro study of neoplastic and neuronal cell differentiation

    Environ. Health Perspect.

    (1989)
  • C. Azar et al.

    Multiple defects of the nerve growth factor receptor in human neuroblastomas

    Prog. Clin. Biol. Res.

    (1991)
  • D.L. Baker et al.

    Analysis of nerve growth factor receptor expression in human neuroblastoma and neuroepithelioma cell lines

    Cancer Res.

    (1989)
  • J.L. Biedler et al.

    Morphology on growth, tumorigenicity and cytogenetics of human neuroblastoma cells in continuous culture

    Cancer Res.

    (1973)
  • S.J. Birren et al.

    Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells

    Science

    (1992)
  • N. Brand et al.

    Identification of a second human retinoic acid receptor

    Nature

    (1988)
  • G.M. Brodeur et al.

    Chromosomal aberrations in human neuroblastoma

    Cancer

    (1977)
  • V. Ciccarone et al.

    Phenotypic diversification in human neuroblastoma cells: expression of neural crest lineages

    Cancer Res.

    (1989)
  • A.M. De Leeuw et al.

    Immunolocalization of cellular retinol-, retinaldehyde- and retinoic acid-binding proteins in rat retina during pre- and postnatal development

    J. Neurocytol.

    (1990)
  • A.J. Durston et al.

    Retinoic acid causes an anteroposterior transformation in the developing central nervous system

    Nature

    (1989)
  • D. Feltner et al.

    Expression of class I histocompatibility antigens in neuroectodermal tumors is independent of the expression of a transfected neuroblastoma myc gene

    J. Immunol.

    (1989)
  • I. Fisher et al.

    Expression and distribution of microtubule-associated protein 2 (MAP2) in neuroblastoma and primary neuronal cells

    Dev. Brain Res.

    (1986)
  • F. Fox et al.

    Maturation of sympathicoblastoma into ganglioneuroma

    Cancer

    (1959)
  • C. Gaetano et al.

    Retinoic acid negatively regulates p34cdc2 expression during human neuroblastoma differentiation

    Cell Growth Diff.

    (1992)
  • C. Gaetano et al.

    In vitro activation of distinct molecular and cellular phenotypes after induction of differentiation in a human neuroblastoma cell line

    Cancer Res.

    (1991)
  • C. Gaetano et al.

    Retinoic acid resistant neuroblastoma cells and the expression of insulin-like growth factor-II

    Adv. Neuroblastoma Res.

    (1991)
  • V. Giguere et al.

    Identification of a receptor for the morphogen retinoic acid

    Nature

    (1987)
  • L.A. Greene et al.

    Establishment of a nonadrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor

  • Cited by (326)

    View all citing articles on Scopus
    View full text