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A 2‐DE MALDI‐TOF study to identify disease regulated serum proteins in lung cancer of c‐myc transgenic mice
Author(s) -
Chatterji Bijon,
Borlak Jürgen
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200701135
Subject(s) - clusterin , apolipoprotein b , transthyretin , microbiology and biotechnology , retinol binding protein 4 , retinol binding protein , biology , orosomucoid , apolipoprotein a1 , cancer research , chemistry , biochemistry , retinol , endocrinology , cholesterol , glycoprotein , apoptosis , insulin resistance , vitamin , insulin , adipokine
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, α‐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 α‐2‐macroglobulin, transthyretin, α‐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.