title: 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.
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.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Fraunhofer ITEM, Hanover, Germany.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Ritorto
authors.forename: Jürgen
authors.initials: J
authors.lastname: Borlak
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D016271:Proto-Oncogene Proteins c-myc / Q000097:blood / Q000235:genetics; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000737:chemistry* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057170:Translational Research, Biomedical
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; C489428:Myc protein, mouse; D009363:Neoplasm Proteins; D011228:Prealbumin; D011506:Proteins; D020543:Proteome; D016271:Proto-Oncogene Proteins c-myc; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; C035737:major urinary proteins; D005979:Glutathione Peroxidase