A 2-DE MALDI-TOF study to identify disease regulated serum proteins in lung cancer of c-myc transgenic mice.
We previously reported targeted overexpression of c-myc to alveolar epithelium to cause lung cancer. We now extended our studies to the serum proteome of tumor bearing mice. Proteins were extracted with a thiourea-containing lysis buffer and separated by 2-DE at pH 4-7 and 3-10 followed by MALDI-TOF/TOF analysis. Forty-six proteins were identified in tumor bearing mice of which n = 9 were statistically significant. This included disease regulated expression of orosomucoid-8, alpha-2-macroglobulin, apolipoprotein-A1, apolipoprotein-C3, glutathione peroxidase-3, plasma retinol-binding protein, and transthyretin, while expression of apolipoprotein-E was decreased at late stages of disease. Moreover, serum amyloid P component was uniquely expressed at late stages of cancer. It is of considerable importance that most disease regulated proteins carried the E-Box sequence (CACGTG) in the promoter of the coding gene, therefore providing evidence for their regulation by c-myc. Notably, expression of alpha-2-macroglobulin, transthyretin, alpha-1-antitrypsin, and properdin was in common in different lung tumor models, but regulation of orosomucoid-8, apolipoprotein-A1, apolipoprotein-C3, apolipoprotein-E, glutathione peroxidase-3, plasma retinol-binding protein, and serum amyloid P component was unique when the serum proteomes of c-myc and c-raf tumor bearing mice were compared. Therefore, candidate biomarkers to differentiate between atypical adenomatous hyperplasias (AAH) and bronchiolo-alveolar carcinomas (BAC)/papillary adenocarcinomas (PLAC) can be proposed.
Chatterji
Bijon
B
Department of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Borlak
Jürgen
J
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D024721:E-Box Elements / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016011:Normal Distribution; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000209:Acute-Phase Proteins; D001053:Apolipoproteins; D015415:Biomarkers; D001798:Blood Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D019908:Proto-Oncogene Proteins c-raf