論文 - 詳細
| RRC ID | 38187 |
|---|---|
| 著者 | Matsubara D, Ishikawa S, Sachiko O, Aburatani H, Fukayama M, Niki T. |
| タイトル | Co-activation of epidermal growth factor receptor and c-MET defines a distinct subset of lung adenocarcinomas. |
| ジャーナル | 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. |
| 巻・号 | 177(5) |
| ページ | 2191-204 |
| 公開日 | 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 |
| 引用数 | 36 |
| WOS 分野 | PATHOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |