Expression of C-terminal ALK, RET, or ROS1 in lung cancer cells with or without fusion
| Autor: | Sei Shu, Marie Mochizuki, Yasushi Yoshimura, Naoki Harada, Mirei Kohno, Koh Furugaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Alectinib Cancer Research Lung Neoplasms Oncogene Proteins Fusion Cell Rearrangement Biology medicine.disease_cause Proto-Oncogene Mas lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Proto-Oncogene Proteins Genetics medicine ROS1 Biomarkers Tumor Anaplastic lymphoma kinase Humans Anaplastic Lymphoma Kinase Epidermal growth factor receptor Fusion Mutation Oncogene Gene Expression Profiling Proto-Oncogene Proteins c-ret Protein-Tyrosine Kinases EML4 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunohistochemistry Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology ALK Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Lung cancer RET Research Article |
| Zdroj: | BMC Cancer, Vol 19, Iss 1, Pp 1-10 (2019) BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-019-5527-2 |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5527-2) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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