title: Gene expression analysis in HBV transgenic mouse liver: a model to study early events related to hepatocarcinogenesis.
abstract: Hepatitis B virus (HBV) is one of the major etiological factors responsible for the development of hepatocellular carcinoma (HCC). We used a transgenic mouse, containing HBV sequences, as a model system to unravel the molecular mechanisms of hepatocarcinogenesis induced by HBV. We chose this animal model because it consistently develops liver cancer after intermediate steps that mimic the natural history of HBV infection in humans. In this study, we focus our attention on the early events leading to liver cancer. We compared the gene expression profile of 3-month-old transgenic mice with that of 3-month-old wild-type (wt) animals. In the transgenic mouse, microarray data analysis showed a total of 45 significantly differentially expressed genes, 25 highly expressed (fold change > or =2; P = 0.0025), and 20 downregulated (fold change < or =0.5; P = 0.0025). These genes belong to several different functional categories such as the regulation of immunological response, transcription, intracellular calcium ion mobilization, regulation of cell cycle and proliferation, NF-kappab signal transduction cascades, and apoptosis. In particular, the upregulation of the antiapoptotic gene NuprI and the downregulation of the proapoptotic gene Bnip3 were found. This observation was supported by an in vitro apoptosis assay that showed downregulation of apoptosis in hepatocytes of HBV transgenic mouse compared with wt mice treated with staurosporine. In conclusion, our experimental approach allowed identification of new genes modulated by HBV and showed that the apoptotic process was deregulated in transgenic mouse hepatocytes. These data shed light on one possible mechanism by which HBV induces hepatocarcinogenesis.
authors.affiliation: Sezione di Gastroenterologia, Dipartimento di Emergenza e di Trapianto d'Organo, Università di Bari, Bari, Italia.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.forename: Daniela
authors.initials: D
authors.lastname: Spano
authors.forename: Maria
authors.initials: M
authors.lastname: D'Apolito
authors.forename: Marta
authors.initials: M
authors.lastname: Centra
authors.forename: Carla
authors.initials: C
authors.lastname: Lasalandra
authors.forename: Mario
authors.initials: M
authors.lastname: Capasso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Diego
authors.initials: D
authors.lastname: Arcelli
authors.forename: Natalia
authors.initials: N
authors.lastname: Rosso
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiribelli
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D019311:Staurosporine