87 145

Cited 18 times in

cMET Activation and EGFR-Directed Therapy Resistance in Triple-Negative Breast Cancer

Authors
 Joohyuk Sohn  ;  Shuying Liu  ;  Napa Parinyanitikul  ;  Jangsoon Lee  ;  Gabriel N. Hortobagyi  ;  Gordon B. Mills  ;  Naoto T. Ueno  ;  Ana M. Gonzalez-Angulo 
Citation
 JOURNAL OF CANCER, Vol.5(9) : 745-753, 2014 
Journal Title
 JOURNAL OF CANCER 
Issue Date
2014
Keywords
EGFR ; Therapy resistance ; Triple-negative breast cancer ; cMET
Abstract
Background: EGFR expression and pathway activation are common in triple-negative breast cancer (TNBC). However, anti-EGFR therapies have not been effective in these patients. We aimed to study the efficacy of targeting MET in overcoming resistance to EGFR therapy in TNBC cell lines. Methods: TNBC lines (MDA-MB-468, HCC-1395, and MDA-MB-231), and a hormone receptor-positive breast cancer line (T47D) were stimulated with epidermal growth factor (EGF) and hepatocyte growth factor (HGF). Lines were then treated with different concentrations of EGFR inhibitors (gefitinib or cetuximab), with or without a MET tyrosine kinase inhibitor (EMD 1214063). Proliferation was measured by MTS assay, in soft agar and with a matrigel assay. Synergy was measured with Calcusyn. Protein expression and signaling were examined with immunoblotting. Results: There was activation of ligand-receptor-downstream signaling pathways in MDA-MB-468 and HCC-1395 upon stimulation with EGF and HGF. In these cell lines, we observed synergism when combining EGFR and MET inhibitors. These results were observed across assays. In western blotting, combination therapy resulted in abrogation of pAKT and pMAPK while monotherapy did not. Conclusion: Our data demonstrate that dual EGFR/MET inhibition is synergistic in TNBC. Targeting both EGFR and MET receptors may provide an effective therapeutic strategy in TNBC.
Files in This Item:
T201403502.pdf Download
DOI
10.7150/jca.9696
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99963
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse