Document Detail


Multiple defects of the nerve growth factor receptor in human neuroblastomas.
MedLine Citation:
PMID:  1963076     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuroblastoma is a tumor of postganglionic sympathetic origin, and nerve growth factor (NGF) is normally required for the survival and differentiation of sympathetic neuroblasts. Since the biological activity of NGF is mediated by the NGF receptor (NGFR), we hypothesized that defects in the NGF/NGFR pathway may play a role in maintenance of the undifferentiated state of neuroblastomas. To test this hypothesis, we examined the structure of the NGFR at the DNA, RNA, and protein levels in a panel of 10 neuroblastoma cell lines. In addition, we examined the function of the NGFR in these lines by analysis of NGF binding kinetics, as well as by the ability of NGF to induce c-fos expression and neurite outgrowth. Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes. Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH, and LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kilobases and Mr approximately 75,000, respectively). NGF binding assays and Scatchard analyses were performed on the four NGFR-positive lines. The NGP line possesses only low-affinity receptor (Kd approximately 3.5 x 10(-9)), whereas the other three lines express both low- and high-affinity forms (Kd approximately 10(-9) and Kd approximately 10(-11), respectively). However, none of the 10 lines exhibited a response to NGF treatment as assayed by c-fos mRNA induction and neurite extension.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
C G Azar; N J Scavarda; C P Reynolds; G M Brodeur
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  1     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1990 Sep 
Date Detail:
Created Date:  1991-04-02     Completed Date:  1991-04-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  421-8     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Northern
Blotting, Southern
Cell Line
DNA, Neoplasm / genetics
Gene Expression
Genes
Humans
Nerve Growth Factors / metabolism,  pharmacology
Neuroblastoma / genetics*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-fos
Proto-Oncogene Proteins c-myc / genetics
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Receptors, Cell Surface / genetics*,  metabolism
Receptors, Nerve Growth Factor
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA-01027/CA/NCI NIH HHS; CA-44904/CA/NCI NIH HHS; CA-49712/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 0/Nerve Growth Factors; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Receptors, Cell Surface; 0/Receptors, Nerve Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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