Cited 10 times in
Reduced expression of EI24 confers resistance to gefitinib through IGF-1R signaling in PC9 NSCLC cells
DC Field | Value | Language |
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dc.contributor.author | 김혜련 | - |
dc.contributor.author | 조병철 | - |
dc.date.accessioned | 2016-02-04T12:04:38Z | - |
dc.date.available | 2016-02-04T12:04:38Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0169-5002 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/141839 | - |
dc.description.abstract | OBJECTIVES: Lung cancer is the commonly diagnosed cancer and is the leading cause of cancer-related mortality worldwide. The most prevalent form of lung cancer is NSCLC, comprising 80% of all lung cancer cases, and epidermal growth factor receptor (EGFR) is frequently mutated in NSCLC. EI24 is a p53-responsive gene and plays an important role in tumor suppression. In the current study, we found that reduced expression of EI24 conferred resistance to EGFR-tyrosine-kinase inhibitor (TKI) in NSCLC cells. MATERIALS AND METHODS: The correlation between EI24 expression and EGFR-TKI drug resistance in EGFR-driven tumors were determined from microarray datasets. The phospho-protein expression profiles of receptor tyrosine kinases and protein kinases were examined using antibody arrays method in PC9 cells expressing shRNAs targeting EI24 and gefitinib-resistant PC9-GR cells expressing exogenous EI24. RESULTS AND CONCLUSIONS: The EGFR-TKI resistant clones had reduced expression of EI24 mRNA compared to the sensitive clones, and EI24 knockdown rendered sensitive cells resistant to EGFR-TKI. Receptor tyrosine kinase screening revealed the involvement of a kinase switch in EI24-mediated regulation of drug sensitivity. We found that EI24 modulates the insulin growth factor-1 receptor (IGF-1R) pathway through the induction of IGF-1. Combination treatment with EGFR and IGF-1R inhibitors significantly reduced the viability of EI24 knockdown-induced resistant cell lines compared to single-agent treatments. We also showed that low EI24 and high IGF-1R expressions in lung cancer patients were correlated with reduced overall survival. Taken together, these results suggest a potential role for EI24 as a biomarker of drug resistance, and indicate that combination therapy with EGFR and IGF-1R inhibitors would be effective in NSCLC patients with low EI24 expression. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 175~181 | - |
dc.relation.isPartOf | LUNG CANCER | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Antineoplastic Agents/pharmacology | - |
dc.subject.MESH | Apoptosis Regulatory Proteins/genetics* | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/drug therapy* | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung/genetics* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Drug Resistance, Neoplasm/drug effects | - |
dc.subject.MESH | Drug Resistance, Neoplasm/genetics | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Insulin/genetics | - |
dc.subject.MESH | Lung Neoplasms/drug therapy* | - |
dc.subject.MESH | Lung Neoplasms/genetics* | - |
dc.subject.MESH | Mutation/drug effects | - |
dc.subject.MESH | Mutation/genetics | - |
dc.subject.MESH | Nuclear Proteins/genetics* | - |
dc.subject.MESH | Protein Kinase Inhibitors/pharmacology | - |
dc.subject.MESH | Protein-Tyrosine Kinases/genetics | - |
dc.subject.MESH | Quinazolines/pharmacology* | - |
dc.subject.MESH | RNA, Messenger/genetics | - |
dc.subject.MESH | Receptor, Epidermal Growth Factor/genetics | - |
dc.subject.MESH | Receptor, IGF Type 1/genetics* | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.title | Reduced expression of EI24 confers resistance to gefitinib through IGF-1R signaling in PC9 NSCLC cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Jung-Min Choi | - |
dc.contributor.googleauthor | Ji-Young Jang | - |
dc.contributor.googleauthor | Han-Woong Lee | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.contributor.googleauthor | Yu-Ra Choi | - |
dc.identifier.doi | 10.1016/j.lungcan.2015.08.019 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J02174 | - |
dc.identifier.eissn | 1872-8332 | - |
dc.identifier.pmid | 26342551 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S016950021530043X | - |
dc.subject.keyword | Drug resistance | - |
dc.subject.keyword | EGFR-TKI | - |
dc.subject.keyword | EI24 | - |
dc.subject.keyword | IGF-1R | - |
dc.subject.keyword | NSCLC | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | Cho, Byoung Chul | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 90 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 175 | - |
dc.citation.endPage | 181 | - |
dc.identifier.bibliographicCitation | LUNG CANCER, Vol.90(2) : 175-181, 2015 | - |
dc.identifier.rimsid | 30912 | - |
dc.type.rims | ART | - |
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