Document Detail

Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors.
MedLine Citation:
PMID:  8987776     Owner:  NLM     Status:  MEDLINE    
Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wild-type uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent. These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors.
Y Muragaki; T T Chou; D R Kaplan; J Q Trojanowski; V M Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  17     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-11-28     Completed Date:  1997-11-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  530-42     Citation Subset:  IM    
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
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MeSH Terms
3T3 Cells
Apoptosis / drug effects*
Brain Neoplasms / pathology*
Cell Cycle
Medulloblastoma / pathology*
Nerve Growth Factors / pharmacology*
Nerve Tissue Proteins / drug effects*,  genetics,  metabolism
Protein Processing, Post-Translational
Proto-Oncogene Proteins / drug effects*,  genetics,  metabolism
Receptor Protein-Tyrosine Kinases / drug effects*,  genetics,  metabolism
Receptor, trkA
Receptors, Nerve Growth Factor / drug effects*,  genetics,  metabolism
Recombinant Fusion Proteins / metabolism
Signal Transduction / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Nerve Growth Factors; 0/Nerve Tissue Proteins; 0/Proto-Oncogene Proteins; 0/Receptors, Nerve Growth Factor; 0/Recombinant Fusion Proteins; EC Protein-Tyrosine Kinases; EC, trkA

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