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Serum proteomics of lung adenocarcinomas induced by targeted overexpression of c-raf in alveolar epithelium identifies candidate biomarkers

 
: Chatterji, B.; Borlak, J.

:
Preprint urn:nbn:de:0011-n-675471 (1.7 MByte PDF)
MD5 Fingerprint: 1b4ec384aa79754c8c38a577f1fe1318
Copyright 2007 Wiley-VCH
Erstellt am: 28.7.2010


Proteomics 7 (2007), Nr.21, S.3980-3991
ISSN: 1615-9853
ISSN: 1615-9861
Englisch
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer ITEM ()
2-DE; biomarkers; C-raf; lung adenocarcinoma; biochemical marker; Serum

Abstract
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.

: http://publica.fraunhofer.de/dokumente/N-67547.html