PMID- 22842573
OWN - NLM
STAT- MEDLINE
DCOM- 20121218
LR  - 20181201
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 425
IP  - 2
DP  - 2012 Aug 24
TI  - BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition.
PG  - 328-32
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - de Farias, Caroline Brunetto
AU  - de Farias CB
AD  - Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), 
      Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
FAU - Heinen, Tiago Elias
AU  - Heinen TE
FAU - dos Santos, Rafael Pereira
AU  - dos Santos RP
FAU - Abujamra, Ana Lucia
AU  - Abujamra AL
FAU - Schwartsmann, Gilberto
AU  - Schwartsmann G
FAU - Roesler, Rafael
AU  - Roesler R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120725
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Brain-Derived Neurotrophic Factor/antagonists & 
      inhibitors/*metabolism/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cetuximab
MH  - Colorectal Neoplasms/*metabolism
MH  - *Drug Resistance, Neoplasm
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - HT29 Cells
MH  - Humans
MH  - Receptor, trkB/antagonists & inhibitors/*metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction
EDAT- 2012/07/31 06:00
MHDA- 2012/12/19 06:00
CRDT- 2012/07/31 06:00
PHST- 2012/07/14 00:00 [received]
PHST- 2012/07/17 00:00 [accepted]
PHST- 2012/07/31 06:00 [entrez]
PHST- 2012/07/31 06:00 [pubmed]
PHST- 2012/12/19 06:00 [medline]
AID - S0006-291X(12)01398-8 [pii]
AID - 10.1016/j.bbrc.2012.07.091 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Aug 24;425(2):328-32. doi: 
      10.1016/j.bbrc.2012.07.091. Epub 2012 Jul 25.