title: Molecular profiling of hepatocellular carcinoma in mice with a chronic deficiency of hepatic s-adenosylmethionine: relevance in human liver diseases.
abstract: S-adenosylmethionine arises as a central molecule in the preservation of liver homeostasis as a chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. In the present work, we have attempted a comprehensive analysis of proteins associated with hepatocarcinogenesis in MAT1A knock out mice using a combination of two-dimensional electrophoresis and mass spectrometry, to then apply the resulting information to identify hallmarks of human HCC. Our results suggest the existence of individual-specific factors that might condition the development of preneoplastic lesions. Proteomic analysis allowed the identification of 151 differential proteins in MAT1A-/- mice tumors. Among all differential proteins, 27 changed in at least 50% of the analyzed tumors, and some of these alterations were already detected months before the development of HCC in the KO liver. The expression level of genes coding for 13 of these proteins was markedly decreased in human HCC. Interestingly, seven of these genes were also found to be down-regulated in a pretumoral condition such as cirrhosis, while depletion of only one marker was assessed in less severe liver disorders.
authors.affiliation: Division of Hepatology and Gene Therapy, CIMA, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Santamaría
authors.forename: Javier
authors.initials: J
authors.lastname: Muñoz
authors.forename: Joaquín
authors.initials: J
authors.lastname: Fernandez-Irigoyen
authors.forename: Laura
authors.initials: L
authors.lastname: Sesma
authors.forename: María I
authors.initials: MI
authors.lastname: Mora
authors.forename: Carmen
authors.initials: C
authors.lastname: Berasain
authors.forename: Shelly C
authors.initials: SC
authors.lastname: Lu
authors.forename: José M
authors.initials: JM
authors.lastname: Mato
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Matías A
authors.initials: MA
authors.lastname: Avila
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Corrales
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010449:Peptide Mapping; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis*; D012436:S-Adenosylmethionine / Q000172:deficiency* / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000494:pharmacology; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D020543:Proteome; D012436:S-Adenosylmethionine; D014357:Trypsin