Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/94020
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
摘要: 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.
URI: http://hdl.handle.net/11455/94020
Appears in Collections:生物醫學研究所

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