| BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition. | |
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MedLine Citation:
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PMID: 22842573 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Caroline Brunetto de Farias; Tiago Elias Heinen; Rafael Pereira dos Santos; Ana Lucia Abujamra; Gilberto Schwartsmann; Rafael Roesler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-07-25 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 425 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-08-27 Completed Date: 2012-12-18 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 328-32 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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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 Humans Receptor, Epidermal Growth Factor / antagonists & inhibitors* Receptor, trkB / antagonists & inhibitors, metabolism* Recombinant Proteins / pharmacology Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Brain-Derived Neurotrophic Factor; 0/Recombinant Proteins; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, trkB; PQX0D8J21J/cetuximab |
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