TY - JOUR
T1 - Gene expression analysis in HBV transgenic mouse liver
T2 - A model to study early events related to hepatocarcinogenesis
AU - Barone, Michele
AU - Spano, Daniela
AU - D'Apolito, Maria
AU - Centra, Marta
AU - Lasalandra, Carla
AU - Capasso, Mario
AU - Di Leo, Alfredo
AU - Volinia, Stefano
AU - Arcelli, Diego
AU - Rosso, Natalia
AU - Francavilla, Antonio
AU - Tiribelli, Claudio
AU - Iolascon, Achille
PY - 2006/4
Y1 - 2006/4
N2 - 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 ≥ 2; P = 0.0025), and 20 downregulated (fold change ≤ 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-κb signal transduction cascades, and apoptosis. In particular, the upregulation of the antiapoptotic gene Nuprl 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.
AB - 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 ≥ 2; P = 0.0025), and 20 downregulated (fold change ≤ 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-κb signal transduction cascades, and apoptosis. In particular, the upregulation of the antiapoptotic gene Nuprl 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.
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U2 - 10.2119/2006-00015.Barone
DO - 10.2119/2006-00015.Barone
M3 - Article
C2 - 16953557
AN - SCOPUS:33748997080
VL - 12
SP - 115
EP - 123
JO - Molecular Medicine
JF - Molecular Medicine
SN - 1076-1551
IS - 4-6
ER -