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標題: Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance
作者: Lin, Chi-Chen
Chen, Jing-Ting
Lin, Meng-Wei
Chan, Chia-Hao
Wen, Yueh-Feng
Wu, Shin-Bei
Chung, Ting-Wen
Lyu, Kevin W
Chou, Hsiu-Chuan
Chan, Hong-Lin
關鍵字: DIGE;Gefitinib;Lung adenocarcinoma;PCNT;Proteomics;Resistance;mPR;Adenocarcinoma;Antigens;Antineoplastic Agents;Carcinoma, Non-Small-Cell Lung;Cell Line, Tumor;Cell Survival;Gene Silencing;Humans;Lung Neoplasms;Membrane Proteins;Proteomics;Quinazolines;RNA, Small Interfering;Receptor, Epidermal Growth Factor;Receptors, Progesterone;Signal Transduction;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Drug Resistance, Neoplasm
Project: Toxicology and applied pharmacology, Volume 288, Issue 3, Page(s) 359-73.
Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12-18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC.
DOI: 10.1016/j.taap.2015.08.008
Appears in Collections:生物醫學研究所

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