6533b83afe1ef96bd12a70a0
RESEARCH PRODUCT
Immunopositivity for histone macroH2A1 isoforms marks steatosisassociated hepatocellular carcinoma.
Nunzia ScibettaLucie BourgoinMarion PeyrouRoger WilliamsValerio PazienzaArianna MarinoGianluigi MazzoccoliFrancesca RappaAzzura GrecoManlio VinciguerraFrancesco CappelloFrancesco CappelloMichelangelo FotiChristine PodriniMassimo Federicisubject
MalePathologyMouseBiological Markers/metabolismEpidemiologyTumor Microenvironment/geneticsColorectal cancerGene ExpressionHepatocytes/metabolism/pathologyNonalcoholic SteatohepatitisHistonesFatty Liver/chemically induced/complications/genetics/metabolismMice0302 clinical medicineGastrointestinal CancersTumor MicroenvironmentPathologyProtein IsoformsDiethylnitrosamineSettore MED/49 - Scienze Tecniche Dietetiche ApplicateMice KnockoutRegulation of gene expression0303 health sciencesMultidisciplinaryProtein Isoforms/genetics/metabolismbiologyLiver DiseasesPTEN Phosphohydrolase/deficiency/geneticshepatocellular carcinoma biomarker histone variant steatosis epigeneticsLiver NeoplasmsQFatty liverRHistone ModificationAnimal ModelsImmunohistochemistry3. Good healthHistoneOncology030220 oncology & carcinogenesisHepatocellular carcinomaMedicineEpigeneticsCarcinoma Hepatocellular/etiology/genetics/metabolism/pathologyResearch ArticleGene isoformmedicine.medical_specialtyCarcinoma HepatocellularHistologyClinical Research DesignScienceGastroenterology and HepatologyDiet High-Fat03 medical and health sciencesModel OrganismsDiagnostic MedicineGastrointestinal TumorsGeneticsCancer GeneticsCancer Detection and DiagnosisEarly DetectionmedicineAnimalsHumansAnimal Models of DiseaseObesityddc:612BiologyHistones/genetics/metabolismNutrition030304 developmental biologyCell NucleusCell Nucleus/genetics/metabolism/pathologyTumor microenvironmentbusiness.industryPTEN PhosphohydrolaseCancers and NeoplasmsHepatocellular Carcinomamedicine.diseasedigestive system diseasesFatty LiverBiomarker EpidemiologyGene Expression RegulationHepatocytesbiology.proteinLiver Neoplasms/etiology/genetics/metabolism/pathologySteatosisbusinessBiomarkersGeneral Pathologydescription
BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously.MethodsWe examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN) and the phosphatase and tensin homolog (PTEN) liver specific knock-out (KO) mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry.ResultsProtein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (pConclusionsThese data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-11-06 |