Combined serum and tissue proteomic study applied to a c-Myc transgenic mouse model of hepatocellular carcinoma identified novel disease regulated proteins suitable for diagnosis and therapeutic intervention strategies.
J Proteome Res
; 10(7): 3012-30, 2011 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-21644509
ABSTRACT
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death in the U.S. Notably, most HCCs display c-Myc hyperactivity but this transcription factor participates in the regulation of as many as 15-20% of genes of the human genome. To better understand its oncogenic activity, a mass spectrometry-based proteomic approach was employed to search for disease-regulated proteins in liver tissue and serum of c-Myc transgenic mice that specifically developed HCC. Overall, a total of 90 differentially expressed proteins were identified with retinol binding protein 4, transthyretin, major urinary protein family, apolipoprotein E, and glutathione peroxidase being regulated in common in tissue and serum of HCC mice. Importantly, this study identified n = 22 novel tumor tissue-regulated proteins to function in cell cycle and proliferation, nucleotide and ribosomal biogenesis, oxidative stress, and GSH metabolism, while bioinformatics revealed the coding sequences of regulated proteins to enharbour c-Myc binding sites. Translation of the findings to human disease was achieved by Western immunoblotting of serum proteins and by immunohistochemistry of human HCC. Taken collectively, our study helps to define a c-Myc proteome suitable for diagnostic and possible therapeutic intervention strategies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Carcinoma Hepatocelular
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Proteômica
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Soro
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Fígado
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Neoplasias Hepáticas
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Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Revista:
J Proteome Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha