Document Detail

Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death.
MedLine Citation:
PMID:  16778834     Owner:  NLM     Status:  MEDLINE    
Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells.
Z Li; J Zhang; Z Liu; C-W Woo; C J Thiele
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2006-06-16
Journal Detail:
Title:  Cell death and differentiation     Volume:  14     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-15     Completed Date:  2007-03-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  318-26     Citation Subset:  IM    
Cell & Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism
Antineoplastic Agents / pharmacology*
Apoptosis Regulatory Proteins / genetics,  metabolism*
Brain-Derived Neurotrophic Factor / pharmacology*
Cell Death / drug effects
Cisplatin / pharmacology
Down-Regulation / drug effects*
Enzyme Activation / drug effects
Etoposide / pharmacology
Forkhead Transcription Factors / metabolism
Gene Expression Regulation, Enzymologic / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Gene Silencing
Membrane Proteins / genetics,  metabolism*
Mitogen-Activated Protein Kinases / metabolism
Molecular Mimicry / drug effects
Neuroblastoma / enzymology*,  genetics,  pathology*
Paclitaxel / pharmacology
Phosphorylation / drug effects
Protein Isoforms / genetics,  metabolism
Proto-Oncogene Proteins / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / metabolism
Receptor, trkB / genetics,  metabolism*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Brain-Derived Neurotrophic Factor; 0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Membrane Proteins; 0/Protein Isoforms; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 15663-27-1/Cisplatin; 33069-62-4/Paclitaxel; 33419-42-0/Etoposide; EC 3-Kinase; EC, trkB; EC Protein Kinases

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

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