title: Comparative proteomic profiling of pancreatic ductal adenocarcinoma cell lines.
abstract: Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and - sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.
authors.affiliation: Departments of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea.
authors.forename: Yikwon
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Departments of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea ; Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Han
authors.affiliation: Departments of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea.
authors.forename: Hophil
authors.initials: H
authors.lastname: Min
authors.affiliation: Departments of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea.
authors.forename: Jonghwa
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul 110-799, Korea.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Yi
authors.affiliation: Departments of Biomedical Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea ; Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799 Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D005978:Glutathione; D000093542:Gemcitabine
keywords: LC-MS/MS; chemoresistance; gemcitabine; pancreatic cancer; quantitative Proteomics