論文 - 詳細
| RRC ID | 57735 |
|---|---|
| 著者 | Furugaki K, Mochizuki M, Kohno M, Shu S, Harada N, Yoshimura Y. |
| タイトル | Expression of C-terminal ALK, RET, or ROS1 in lung cancer cells with or without fusion. |
| ジャーナル | BMC Cancer |
| Abstract |
BACKGROUND:Genetic alterations, including mutation of epidermal growth factor receptor or v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog and fusion of anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), or v-ros UR2 sarcoma virus oncogene homolog 1 (ROS1), occur in non-small cell lung cancers, and these oncogenic drivers are important biomarkers for targeted therapies. A useful technique to screen for these fusions is the detection of native carboxy-terminal (C-terminal) protein by immunohistochemistry; however, the effects of other genetic alterations on C-terminal expression is not fully understood. In this study, we evaluated whether C-terminal expression is specifically elevated by fusion with or without typical genetic alterations of lung cancer. METHODS:In 37 human lung cancer cell lines and four tissue specimens, protein and mRNA levels were measured by capillary western blotting and reverse transcription-PCR, respectively. RESULTS:Compared with the median of all 37 cell lines, mRNA levels at the C-terminus of all five of the fusion-positive cell lines tested (three ALK, one RET, and one ROS1) were elevated at least 2000-, 300-, or 2000-fold, respectively, and high C-terminal protein expression was detected. In an ALK fusion-positive tissue specimen, the mRNA and protein levels of C-terminal ALK were also markedly elevated. Meanwhile, in one of 36 RET fusion-negative cell lines, RET mRNA levels at the C-terminus were elevated at least 500-fold compared with the median of all 37 cell lines, and high C-terminal protein expression was detected despite the absence of RET fusion. CONCLUSIONS:This study of 37 cell lines and four tissue specimens shows the detection of C-terminal ALK or ROS1 proteins could be a comprehensive method to determine ALK or ROS1 fusion, whereas not only the detection of C-terminal RET protein but also other methods would be needed to determine RET fusion. |
| 巻・号 | 19(1) |
| ページ | 301 |
| 公開日 | 2019-4-3 |
| DOI | 10.1186/s12885-019-5527-2 |
| PII | 10.1186/s12885-019-5527-2 |
| PMID | 30943926 |
| PMC | PMC6446279 |
| MeSH | Anaplastic Lymphoma Kinase / chemistry Anaplastic Lymphoma Kinase / genetics* Anaplastic Lymphoma Kinase / metabolism Biomarkers, Tumor / genetics Cell Line, Tumor Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / genetics* Lung Neoplasms / metabolism Oncogene Proteins, Fusion / genetics Protein-Tyrosine Kinases / chemistry Protein-Tyrosine Kinases / genetics* Protein-Tyrosine Kinases / metabolism Proto-Oncogene Mas Proto-Oncogene Proteins / chemistry Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-ret / chemistry Proto-Oncogene Proteins c-ret / genetics* Proto-Oncogene Proteins c-ret / metabolism Up-Regulation* |
| IF | 3.15 |
| 引用数 | 2 |
| リソース情報 | |
| ヒト・動物細胞 | B901L(RCB3530) II-18(RCB2093) LC-2/ad(RCB0440) A529L(RCB2817) |