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
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje