title: Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance.
abstract: 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.
authors: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan; Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors: Chi-Chen
authors: CC
authors: Lin
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Jing-Ting
authors: JT
authors: Chen
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors: Meng-Wei
authors: MW
authors: Lin
authors: Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan.
authors: Chia-Hao
authors: CH
authors: Chan
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
authors: Yueh-Feng
authors: YF
authors: Wen
authors: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors: Shin-Bei
authors: SB
authors: Wu
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Ting-Wen
authors: TW
authors: Chung
authors: Lutheran Medical Center, Brooklyn, NY, USA; Global Scholars Program, St. George's University/Northumbria University, Newcastle upon Tyne, United Kingdom.
authors: Kevin W
authors: KW
authors: Lyu
authors: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan. Electronic address: chouhc@mail.nhcue.edu.tw.
authors: Hsiu-Chuan
authors: HC
authors: Chou
authors: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: hlchan@life.nthu.edu.tw.
authors: Hong-Lin
authors: HL
authors: Chan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D000077156:Gefitinib; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011799:Quinazolines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000941:Antigens; D000970:Antineoplastic Agents; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D011799:Quinazolines; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; C086178:pericentrin; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: DIGE; Gefitinib; Lung adenocarcinoma; PCNT; Proteomics; Resistance; mPR