Expression of TrkA, TrkB and TrkC in human neuroblastomas.
There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors of the peripheral nervous system. Evidence from several independent studies suggests that high expression of TrkA is an indicator of favorable outcome, and there is an inverse correlation between TrkA expression and N-myc amplification. In addition, some primary neuroblastomas differentiate in vitro in the presence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification and may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, Trk-C is expressed in favorable neuroblastomas, essentially all of which also express TrkA. In summary, the study of neurotrophin receptor expression and function in neuroblastomas may provide important insights into the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attractive targets for the development of therapy aimed at inducing differentiation or programmed cell death in these tumors.
Brodeur
G M
GM
Division of Oncology, Children's Hospital of Philadelphia, PA, USA.
Nakagawara
A
A
Yamashiro
D J
DJ
Ikegaki
N
N
Liu
X G
XG
Azar
C G
CG
Lee
C P
CP
Evans
A E
AE
D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D016207:Cytokines / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D000078792:Midkine; D008934:Mitogens / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D009447:Neuroblastoma; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D016207:Cytokines; D008934:Mitogens; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C066845:pleiotrophin; D000078792:Midkine; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC