PMID- 10994551
OWN - NLM
STAT- MEDLINE
DCOM- 20001017
LR  - 20151119
IS  - 0300-8630 (Print)
IS  - 0300-8630 (Linking)
VI  - 212
IP  - 4
DP  - 2000 Jul-Aug
TI  - Prognostic and biological role of neurotrophin-receptor TrkA and TrkB in 
      neuroblastoma.
PG  - 200-5
AB  - Expression of different neurotrophin receptors of the tyrosine kinase (Trk) 
      family plays an important role in the biology and clinical behavior of 
      neuroblastomas (NB). Observations from several independent studies suggest that 
      high expression of TrkA is present in NB with favorable biological features and 
      highly correlated with patient survival, whereas TrkB is mainly expressed on 
      unfavorable, aggressive NB with MYCN-amplification. To determine expression of 
      Trk receptors and ligands in primary NB, we developed a reliable semiquantitative 
      duplex RT-PCR protocol, that requires only 1 microgram RNA per tumor sample. 
      Activation of TrkA by its ligand nerve growth factor (NGF) initiates a cascade of 
      signaling events and promotes neuronal differentiation in vitro. Activation of 
      TrkB by its ligand brain derived neurotrophic factor (BDNF) has been associated 
      with proliferation and survival of NB cells. To study Trk signal transduction 
      pathways and their biological effects in NB, we stably expressed TrkA and TrkB 
      cDNA in the human NB cell line SH-SY5Y. Introduction of TrkA and TrkB restored 
      responsiveness of SH-SY5Y cells to the ligands NGF and BDNF, respectively, and 
      resulted in morphological differentiation. Expression of TrkA resulted in growth 
      inhibition of the transfectants compared to parental cells, whereas TrkB 
      transfectants demonstrated an increased proliferation rate. Further insight into 
      the differences of TrkA and TrkB signaling may suggest new options for the 
      treatment of NB. As expression of TrkA is a strong prognostic factor especially 
      in MYCN non-amplified NB, a prospective study of Trk receptor expression using 
      RT-PCR should be performed for German neuroblastoma patients.
FAU - Eggert, A
AU  - Eggert A
AD  - Children's Hospital of Philadelphia/Department of Pediatrics, University of 
      Pennsylvania 19104, USA. angelika.eggert@uni-essen.de
FAU - Ikegaki, N
AU  - Ikegaki N
FAU - Liu, X G
AU  - Liu XG
FAU - Brodeur, G M
AU  - Brodeur GM
LA  - eng
GR  - NS 34514/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Klin Padiatr
JT  - Klinische Padiatrie
JID - 0326144
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Differentiation
MH  - Cell Division
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Vitro Techniques
MH  - Nerve Growth Factor/metabolism
MH  - Neuroblastoma/diagnosis/*metabolism
MH  - Prognosis
MH  - Receptor, trkA/genetics/*metabolism
MH  - Receptor, trkB/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Signal Transduction
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2000/09/20 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/09/20 11:00
PHST- 2000/09/20 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/09/20 11:00 [entrez]
AID - 10.1055/s-2000-9677 [doi]
PST - ppublish
SO  - Klin Padiatr. 2000 Jul-Aug;212(4):200-5. doi: 10.1055/s-2000-9677.