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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apolipoproteins E / blood
-
Apolipoproteins E / genetics
-
Biomarkers / blood
-
Blotting, Western
-
Carcinoma, Hepatocellular / blood
-
Carcinoma, Hepatocellular / diagnosis*
-
Carcinoma, Hepatocellular / genetics*
-
Carcinoma, Hepatocellular / pathology
-
Disease Models, Animal
-
Electrophoresis, Gel, Two-Dimensional
-
Gene Expression Regulation, Neoplastic*
-
Glutathione Peroxidase / blood
-
Glutathione Peroxidase / genetics
-
Humans
-
Immunohistochemistry
-
Liver / chemistry*
-
Liver / metabolism
-
Liver / pathology
-
Liver Neoplasms / blood
-
Liver Neoplasms / diagnosis*
-
Liver Neoplasms / genetics*
-
Liver Neoplasms / pathology
-
Mice
-
Mice, Transgenic
-
Molecular Targeted Therapy
-
Neoplasm Proteins / genetics*
-
Neoplasm Proteins / metabolism
-
Oligonucleotide Array Sequence Analysis
-
Prealbumin / genetics
-
Prealbumin / metabolism
-
Proteins / genetics
-
Proteins / metabolism
-
Proteome / genetics
-
Proteomics / methods*
-
Proto-Oncogene Proteins c-myc / blood
-
Proto-Oncogene Proteins c-myc / genetics
-
Retinol-Binding Proteins, Plasma / genetics
-
Retinol-Binding Proteins, Plasma / metabolism
-
Serum / chemistry*
-
Serum / metabolism
-
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
-
Translational Research, Biomedical
Substances
-
Apolipoproteins E
-
Biomarkers
-
Myc protein, mouse
-
Neoplasm Proteins
-
Prealbumin
-
Proteins
-
Proteome
-
Proto-Oncogene Proteins c-myc
-
Rbp4 protein, mouse
-
Retinol-Binding Proteins, Plasma
-
major urinary proteins
-
Glutathione Peroxidase