Document Detail

BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition.
MedLine Citation:
PMID:  22842573     Owner:  NLM     Status:  MEDLINE    
The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling can protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.
Caroline Brunetto de Farias; Tiago Elias Heinen; Rafael Pereira dos Santos; Ana Lucia Abujamra; Gilberto Schwartsmann; Rafael Roesler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-25
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  425     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-12-18     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  328-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Brain-Derived Neurotrophic Factor / antagonists & inhibitors,  metabolism*,  pharmacology
Cell Proliferation / drug effects
Cell Survival / drug effects
Colorectal Neoplasms / metabolism*
Drug Resistance, Neoplasm*
HT29 Cells
Receptor, Epidermal Growth Factor / antagonists & inhibitors*
Receptor, trkB / antagonists & inhibitors,  metabolism*
Recombinant Proteins / pharmacology
Signal Transduction
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Brain-Derived Neurotrophic Factor; 0/Recombinant Proteins; EC, Epidermal Growth Factor; EC, trkB; PQX0D8J21J/cetuximab

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