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Background/Aims: Transgenic mice that express HBV X protein (HBx) have increased sensitivity to hepatocarcinogens. In the present study, we hypothesized that HBx interferes with the DNA protective increases in telomerase activity that occur in proliferating hepatocytes.Methods: Male CD-1 mice (4–6/grp) were killed and hepatic telomerase activity measured at 0, 6, 12, 24, 36, 48 h post partial hepatectomy (PHx). Four HBx transgenic mice were killed at 12 h post-PHx when maximum telomerase activity was observed in CD-1 non-transgenic mice. mRNA of the telomerase catalytic subunit; murine telomerase reverse transcriptase (mTERT), was measured by reverse transcription-polymerase chain reaction. Telomerase activity and human TERT (hTERT) were also measured in Chang and PLC/PRF/5 cells following transient transfection with HBx cDNA.Results: Telomerase activity peaked at 12 h post-PHx in normal mice, however, in HBx transgenic mice, telomerase activity was significantly lower, both at baseline (P<0.05) and 12 h post-PHx (P<0.01). Following PHx, mTERT mRNA expression remained constant in normal mice but decreased significantly (P<0.01) in HBx transgenic mice. Transfection of HBx in Chang and PLC/PRF/5 cells had no effect on telomerase activity or hTERT mRNA expression.Conclusions: The results of this study suggest that HBx expression may play a role in hepatocellular carcinogenesis by interfering with telomerase activity during hepatocyte proliferation. [Copyright &y& Elsevier]

Background/Aims: When a loss of hepatic mass occurs, the expression of a large number of genes is either induced or altered, accompanying hepatocyte proliferation. In the present study, we made an in-house cDNA microarray containing 4608 elements (Liver chip), and analyzed extensively gene expression profiles of the regenerating liver after 70% partial hepatectomy (PHx) in rats.Methods: RNAs were prepared from three rat livers at each time point (taken at 0, 6, 12, 18, 24, 48, 72 h, and 1 week after PHx). Using the liver chip, we performed large-scale analysis of gene expression during liver regeneration. Elements either up- or down-regulated more than twofold at one or more time points were selected.Results: Among the 4608, 382 were identified. Using cluster analysis, we found great similarity between gene-expression profiles at 12 and 18 h after PHx as well as between 48 and 72 h after PHx. We also found that there are at least six distinct temporal patterns of gene expression in the regenerating rat liver after PHx.Conclusions: These results indicated that microarray analysis is a powerful approach for monitoring molecular events in the regenerating liver. [Copyright &y& Elsevier]