Serum proteomics of lung adenocarcinomas induced by targeted overexpression of c-raf in alveolar epithelium identifies candidate biomarkers.
We previously reported a proteome map of lung adenocarcinomas in serine-threonine kinase of the Raf family (c-raf) transgenic mice. We now extend our initial studies to serum proteins at early stage (1 month) and advanced stages of tumorigenesis (12 months). Notably, serum proteins from wild-type and tumor bearing mice were extracted with a lysis buffer containing 5 mol/L urea, 2 mol/L thiourea, 40 mmol/L Tris, 4% CHAPS, 100 mmol/L DTT, 0.5% BioLyte 3-10, separated by 2-DE and studied by image analysis. On average 400 protein spots per gel were excised and analyzed by MALDI-TOF MS. We identified 45 common and 5 uniquely expressed proteins in wild-type and tumor bearing mice. Apart from uniquely identified proteins we observed for n = 9 proteins differential expression when wild-type and tumor bearing mice were compared. This included serpins and other protease inhibitors, lipocalins, transthyretins, globins, and Igs. Notably, we demonstrate significant regulation of alpha-1-antitrypsin, alpha-2-macroglobulin, hemoglobin subunit alpha, vitamin D-binding protein, major urinary proteins, and transthyretin (up to eight-fold) in serum of lung tumor bearing mice. Disease association of these proteins in human malignancies has been reported. Thus, an identification of regulated serum proteins in this lung cancer disease model provides excellent opportunities for the search of novel biomarkers.
Chatterji
Bijon
B
Department of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Borlak
Jürgen
J
D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000097:blood; D010455:Peptides / Q000235:genetics; D040901:Proteomics / Q000379:methods; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; C489680:Sftpc protein, mouse; D019908:Proto-Oncogene Proteins c-raf