RRC ID 38187
Author Matsubara D, Ishikawa S, Sachiko O, Aburatani H, Fukayama M, Niki T.
Title Co-activation of epidermal growth factor receptor and c-MET defines a distinct subset of lung adenocarcinomas.
Journal Am J Pathol
Abstract Epidermal growth factor receptor (EGFR) and MET are molecular targets for lung cancer treatment. The relationships between expression, activation, and gene abnormalities of these two targets are currently unclear. Here, we demonstrate that a panel of 40 lung cancer cell lines could be classified into two groups. Group I was characterized by (1) high phosphorylations of MET and EGFR, (2) frequent mutation or amplification of EGFR, MET, and human epidermal growth factor receptor-2 (HER2), (3) high expressions of bronchial epithelial markers (thyroid transcription factor-1 (TTF-1), MUC1, and Cytokeratin 7 (CK7)); and (4) high expressions of MET, human epidermal growth factor receptor-3, E-cadherin, cyclooxygenase-2, and laminin gamma2. In contrast, Group II exhibited little or no phosphorylation of MET and EGFR; no mutation or amplification of EGFR, MET, and HER2; were triple-negative for TTF-1, MUC1, and CK7; and showed high expressions of vimentin, fibroblast growth factor receptor-1, and transcription factor 8. Importantly, Group I was more sensitive to gefitinib and more resistant to cisplatin and paclitaxel than Group II. The clinical relevance was confirmed in publicly available data on 442 primary lung adenocarcinoma patients; survival benefits by postoperative chemotherapy were seen in only patients with tumors corresponding to Group II. Overall, co-activation of EGFR and MET defines a distinct subgroup of lung carcinoma with characteristic genetic abnormalities, gene expression pattern, and response to chemotherapeutic reagents.
Volume 177(5)
Pages 2191-204
Published 2010-11-1
DOI 10.2353/ajpath.2010.100217
PII S0002-9440(10)60273-8
PMID 20934974
PMC PMC2966779
MeSH Adenocarcinoma / classification Adenocarcinoma / metabolism* Animals Antineoplastic Agents / pharmacology Biomarkers, Tumor / metabolism Cell Line, Tumor / drug effects Cell Proliferation Cisplatin / pharmacology Cluster Analysis Enzyme Activation ErbB Receptors / genetics ErbB Receptors / metabolism* Gefitinib Gene Expression Profiling Humans Lung Neoplasms / classification Lung Neoplasms / metabolism* Oligonucleotide Array Sequence Analysis Paclitaxel / pharmacology Phenotype Polymorphism, Single Nucleotide Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-met / genetics Proto-Oncogene Proteins c-met / metabolism* Proto-Oncogene Proteins p21(ras) Quinazolines / pharmacology Receptor, ErbB-2 / genetics Receptor, ErbB-2 / metabolism ras Proteins / genetics ras Proteins / metabolism
IF 3.491
Times Cited 36
Human and Animal Cells