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- W2058885931 abstract "Naturally occurring mutants with a deletion in the pre-S2 region of the large surface protein (ΔS2-LHBs) are prevalent in serum and livers of patients with chronic hepatitis B virus (HBV) infection associated with cirrhosis. The ΔS2-LHBs protein is retained in the endoplasmic reticulum (ER) and may induce ER stress. One interesting observation is the consistently clustered distribution of hepatocytes expressing ΔS2-LHBs. In this study, complementary DNA microarray analysis identified cyclin A and several groups of genes as being significantly upregulated by ΔS2-LHBs in the HuH-7 cell line. This observation was confirmed in liver tissues. The induction of cyclin A expression may occur via the specific transactivator function of ΔS2-LHBs independent of ER stress. In the presence of ΔS2-LHBs, hepatocytes sustained cyclin A expression and cell cycle progression under ER stress and displayed increased BrdU incorporation with multinuclear formation. Furthermore, ΔS2-LHBs could enhance anchorage-independent cell growth in a nontransformed human hepatocyte line and induced nodular proliferation of hepatocytes in transgenic mice. In conclusion, these in vitro and in vivo data support a role for ΔS2-LHBs in the hepatocyte hyperplasia and a likely role in the process of HBV-related tumorigenesis. (HEPATOLOGY 2005.)" @default.
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- W2058885931 date "2005-01-01" @default.
- W2058885931 modified "2023-10-16" @default.
- W2058885931 title "Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes" @default.
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- W2058885931 doi "https://doi.org/10.1002/hep.20615" @default.
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