HBsAg andHBx knocked into thep21 locus causes hepatocellular carcinoma in mice
Open Access
- 30 January 2004
- journal article
- viral hepatitis
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 39 (2), 318-324
- https://doi.org/10.1002/hep.20076
Abstract
Hepatocellular carcinoma (HCC) affects males in a significantly higher proportion than females and is one of the human cancers etiologically related to viral factors. Many studies provide strong evidence of the direct role that hepatitis B virus (HBV) plays in hepatic carcinogenesis, but the functions of HBV surface antigen (HBsAg) and X protein (HBx) in hepatocarcinogenesis through direct or indirect mechanisms are still being debated. We generated two HBV gene knock-in transgenic mouse lines by homologous recombination. HBsAg and HBx genes were integrated into the mouse p21 locus. Both male and female p21-HBx transgenic mice developed HCC after the age of 18 months; however, male p21-HBsAg transgenic mice began to develop HCC 3 months earlier. The expression of a number of genes related to metabolism and genomic instability largely resembled the molecular changes during the development of HCC in humans. ER-β (estrogen receptor-β) was extremely up-regulated only in tumor tissues of male p21-HBsAg mice, providing genetic evidence that HBsAg might be the major risk factor affecting the gender difference in the causes of HCC. In conclusion, these mice might serve as good models for studying the different roles of HBsAg and HBx in early events of HBV-related hepatocarcinogenesis. (HEPATOLOGY 2004;39:318–324.)This publication has 27 references indexed in Scilit:
- High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: A multicenter randomized controlled trialHepatology, 2002
- Proteomic analysis and molecular characterization of tissue ferritin light chain in hepatocellular carcinomaHepatology, 2002
- Expression of estrogen receptor-α and -β mRNAs in human gastric cancerCancer Letters, 2002
- The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas apoptosis in the liverOncogene, 2002
- Calcium Signaling by HBx Protein in Hepatitis B Virus DNA ReplicationScience, 2001
- Natural history of inoperable hepatocellular carcinoma: Estrogen receptors' status in the tumor is the strongest prognostic factor for survivalHepatology, 2000
- Cloning of a novel receptor expressed in rat prostate and ovary.Proceedings of the National Academy of Sciences of the United States of America, 1996
- High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic miceHepatology, 1994
- Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic miceCell, 1989
- Compact organization of the hepatitis B virus genomeHepatology, 1989