The HBx gene of hepatitis B virus has been shown to induce hepatic tumors in transgenic mice and is implicated in hepatocarcinogenesis in human hepatitis B virus infection. To further characterize the role of HBx gene in carcinogenesis, we established mouse fibroblast cell lines in which the expression of HBx gene could be controlled by glucocorticoid hormone and examined the effect of HBx gene expression on cell growth in vitro. Along with the expression of HBx gene, most cells in the G0/G1 phase moved into the S phase in 24 h, and the cell cycle progressed further toward 48 h. Induction of DNA synthesis was also demonstrated by bromo-deoxyuridine labeling analysis. These results indicate that HBx gene has a function to trigger the synthesis of cellular DNA and suggest that HBx gene may play a role in hepatocarcinogenesis in human infection by driving deregulated cell cycle progression.
K Koike, K Moriya, H Yotsuyanagi, S Iino, K Kurokawa
Title and authors | Publication | Year |
---|---|---|
Dysregulation of Liver Regeneration by Hepatitis B Virus Infection: Impact on Development of Hepatocellular Carcinoma.
Park ES, Dezhbord M, Lee AR, Park BB, Kim KH |
Cancers | 2022 |
HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G 1 /S cycle
Y Lei, X Xu, H Liu, L Chen, H Zhou, J Jiang, Y Yang, B Wu |
Autophagy | 2021 |
HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA
K Sekiba, M Otsuka, K Funato, Y Miyakawa, E Tanaka, T Seimiya, M Yamagami, T Tsutsumi, K Okushin, K Miyakawa, A Ryo, K Koike |
Journal of Hepatology | 2021 |
The Way to Decoding Pathogenesis and Conquering of National Afflictions, Viral Hepatitis and Liver Cancer.
Koike K |
2021 | |
Relevance of reactive oxygen species in liver disease observed in transgenic mice expressing the hepatitis B virus X protein
DY Yu |
Laboratory animal research | 2020 |
Hepatitis B Virus-X Downregulates Expression of Selenium Binding Protein 1
YM Lee, S Kim, RY Park, YS Kim |
Viruses | 2020 |
The Way to Decoding and Conquering the Pathogenesis of National Affliction, Hepatitis and Liver Cancer
K Koike |
Nihon Naika Gakkai Zasshi | 2017 |
Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma
CC Chao |
World journal of hepatology | 2016 |
Hepatitis B Virus Core Promoter A1762T/G1764A (TA)/T1753A/T1768A Mutations Contribute to Hepatocarcinogenesis by Deregulating Skp2 and P53
J Yan, Z Yao, K Hu, Y Zhong, M Li, Z Xiong, M Deng |
Digestive Diseases and Sciences | 2015 |
Cell Cycle Control
E Noguchi, MC Gadaleta |
Cell Cycle Control | 2014 |
Cell Cycle Control
E Noguchi, MC Gadaleta |
Cell Cycle Control | 2014 |
Cell Cycle Control
E Noguchi, MC Gadaleta |
Cell Cycle Control | 2014 |
HBV induced HCC: major risk factors from genetic to molecular level
A Ayub, UA Ashfaq, A Haque |
BioMed Research International | 2013 |
Hepatitis B virus inhibits liver regeneration via epigenetic regulation of urokinase-type plasminogen activator
ES Park, YK Park, CY Shin, SH Park, SH Ahn, DH Kim, KH Lim, SY Kwon, KP Kim, SI Yang, BL Seong, KH Kim |
Hepatology | 2013 |
The role of the hepatitis viruses in cholangiocarcinoma
S Ralphs, SA Khan |
Journal of Viral Hepatitis | 2013 |
Hepatitis B virus regulatory HBx protein binding to DDB1 is required but is not sufficient for maximal HBV replication
AA Hodgson, JM Hyser, VV Keasler, Y Cang, BL Slagle |
Virology | 2012 |
A zebrafish model of intrahepatic cholangiocarcinoma by dual expression of hepatitis B virus X and hepatitis C virus core protein in liver
W Liu, JR Chen, CH Hsu, YH Li, YM Chen, CY Lin, SJ Huang, ZK Chang, YC Chen, CH Lin, HY Gong, CC Lin, K Kawakami, JL Wu |
Hepatology | 2012 |
Tackling hepatitis B virus-associated hepatocellular carcinoma—the future is now
M Bharadwaj, G Roy, K Dutta, M Misbah, M Husain, S Hussain |
Cancer and Metastasis Reviews | 2012 |
Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH
I Qadri, K Fatima, H AbdeL-Hafiz |
BMC Microbiology | 2011 |
The X protein of hepatitis B virus activates hepatoma cell proliferation through repressing melanoma inhibitory activity 2 gene
Y Xu, Y Yang, Y Cai, F Liu, Y Liu, Y Zhu, J Wu |
Biochemical and Biophysical Research Communications | 2011 |
Analysis of hepatitis B virus X gene (HBx) mutants in tissues of patients suffered from hepatocellular carcinoma in China
Q Wang, T Zhang, L Ye, W Wang, X Zhang |
Cancer Epidemiology | 2011 |
Hepatitis B virus X protein upregulates tumor necrosis factor-α expression of rat mesangial cell line via ERKs pathway
HZ Lu, D Liu, QH Fan, JH Zhou |
Frontiers of Medicine in China | 2010 |
Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: Evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation
F Molina-Jiménez, I Benedicto, M Murata, S Martín-Vílchez, T Seki, JA Pintor-Toro, M Tortolero, R Moreno-Otero, K Okazaki, K Koike, JL Barbero, K Matsuzaki, PL Majano, M López-Cabrera |
Hepatology | 2010 |
Pro-apoptotic function of hepatitis B virus X protein
KH Kim |
The Korean Journal of Hepatology | 2010 |
Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression
TC Kuo, CC Chao |
Biochemical Pharmacology | 2010 |
The Hepatitis B Virus X Protein Modulates Hepatocyte Proliferation Pathways To Stimulate Viral Replication
TL Gearhart, MJ Bouchard |
Journal of virology | 2010 |
Viral transformation and aneuploidy
J Yasunaga, KT Jeang |
Environmental and Molecular Mutagenesis | 2009 |
Sulfasalazine induces apoptosis of HBx-expressing cells in an NF-κB-independent manner
YM Lee, M Kang, JM Hwang, S Lee, H Cho, YS Kim |
Virus Genes | 2009 |
Transcription Factors
IM Adcock, G Caramori |
Asthma and COPD | 2009 |
Premature cell cycle entry induced by hepatitis B virus regulatory HBx protein during compensatory liver regeneration
AJ Hodgson, VV Keasler, BL Slagle |
Cancer research | 2008 |
Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China
X Guo, Y Jin, G Qian, H Tu |
Journal of Hepatology | 2008 |
Id-1 Induces Proteasome-dependent Degradation of the HBX Protein
MT Ling, YT Chiu, TK Lee, SC Leung, MK Fung, X Wang, KF Wong, YC Wong |
Journal of Molecular Biology | 2008 |
Role of hypoxia-inducible factor-α in hepatitis-B-virus X protein-mediated MDR1 activation
HK Han, CY Han, EP Cheon, J Lee, KW Kang |
Biochemical and Biophysical Research Communications | 2007 |
Perspectives in Medical Virology
KD Mena |
Perspectives in Medical Virology | 2007 |
Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis B virus X protein transgenic mice
BK Wu, CC Li, HJ Chen, JL Chang, KS Jeng, CK Chou, MT Hsu, TF Tsai |
Biochemical and Biophysical Research Communications | 2006 |
RNAi-Based Knockdown of HBx mRNA in HBx-Transformed and HBV-Producing Human Liver Cells
YH Kim, JH Lee, NW Paik, HM Rho |
DNA and Cell Biology | 2006 |
Increased liver pathology in hepatitis C virus transgenic mice expressing the hepatitis B virus X protein
VV Keasler, H Lerat, CR Madden, MJ Finegold, MJ McGarvey, EM Mohammed, SJ Forbes, SM Lemon, DL Hadsell, SJ Grona, FB Hollinger, BL Slagle |
Virology | 2006 |
Effects of hepatitis B virus X protein on the development of liver cancer
X Zhang, H Zhang, L Ye |
Journal of Laboratory and Clinical Medicine | 2006 |
The Molecular Diagnosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma
CH Wong, SK Chan, HL Chan, SK Tsui |
Critical Reviews in Clinical Laboratory Sciences | 2006 |
Differential effects on apoptosis induction in hepatocyte lines by stable expression of hepatitis B virus X protein
N Fiedler |
World journal of gastroenterology : WJG | 2006 |
Impact of transforming viruses on cellular mutagenesis, genome stability, and cellular transformation
ML Gatza, C Chandhasin, RI Ducu, SJ Marriott |
Environmental and Molecular Mutagenesis | 2005 |
An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells
YH Jin, MH Kwon, K Kim, HJ Shin, JS Shin, H Cho, S Park |
Cancer Immunology, Immunotherapy | 2005 |
A case of recurrent hepatocellular carcinoma, based on different hepatic pathogenesis from initial condition, developed 18 years after hepatic resection
M ITSUBO, K KOIKE, M OSADA, S KOBAYASHI |
Kanzo | 2005 |
Identification of hepatitis B virus X gene mutation in Hong Kong patients with hepatocellular carcinoma
GG Chen, MY Li, RL Ho, EC Chak, WY Lau, PB Lai |
Journal of Clinical Virology | 2005 |
The Hepatitis B Virus X Protein Sensitizes HepG2 Cells to UV Light-induced DNA Damage
AT Lee, J Ren, ET Wong, KH Ban, LA Lee, CG Lee |
The Journal of biological chemistry | 2005 |
cDNA microarray analysis of early gene expression profiles associated with hepatitis B virus X protein-mediated hepatocarcinogenesis
RK Ng, CY Lau, SM Lee, SK Tsui, KP Fung, MM Waye |
Biochemical and Biophysical Research Communications | 2004 |
Transfection and expression of hepatitis B virus x gene and its effect on apoptosis in HL-7702 cells
HY Chen, NH Tang, XJ Li, SJ Zhang, ZX Chen, XZ Wang |
World journal of gastroenterology : WJG | 2004 |
Handbook of Cancer Vaccines
MA Morse, TM Clay, HK Lyerly |
2004 | |
Detection of the hepatitis B virus X protein (HBx) antigen and anti-HBx antibodies in cases of human hepatocellular carcinoma
GY Hwang, CY Lin, LM Huang, YH Wang, JC Wang, CT Hsu, SS Yang, CC Wu |
Journal of clinical microbiology | 2003 |
Molecular Aspects of Hepatitis B Viral Infection and the Viral Carcinogenesis
WS Ryu |
Journal of Biochemistry and molecular biology | 2003 |
A Critical Evaluation of DNA Adducts as Biological Markers for Human Exposure to Polycyclic Aromatic Compounds
RW Godschalk, FJ Schooten, H Bartsch |
Journal of Biochemistry and molecular biology | 2003 |
Dominant mutations of hepatitis B virus variants in hepatoma accumulate in B-cell and T-cell epitopes of the HBx antigen
GY Hwang, CJ Huang, CY Lin, CC Wu |
Virus Research | 2003 |
Implicación de la proteína HBx del virus de la hepatitis B en la respuesta inmune y la progresión tumoral
E Lara-Pezzi, R Moreno-Otero, M López-Cabrera |
Gastroenterología y Hepatología | 2003 |
Hepatitis B virus X protein induces TNF-alpha expression via down-regulation of selenoprotein P in human hepatoma cell line, HepG2
Young-Su Yi, Sung Gyoo Park, Sung Moo Byeon, Young-Guen Kwon, Guhung Jung |
Biochimica et Biophysica Acta | 2003 |
Expression of hepatitis B virus X protein in transgenic mice
Jun Xiong, Yu-Cheng Yao, Xiao-Yuan Zi, Jian-Xiu Li, Xin-Min Wang, Xu-Ting Ye, Shu-Min Zhao, Yong-Bi Yan, Hong-Yu Yu, Yi-Ping Hu |
World journal of gastroenterology : WJG | 2003 |
Hepatitis B virus X protein regulates transactivation activity and protein stability of the cancer-amplified transcription coactivator ASC-2
H Kong |
Hepatology | 2003 |
Expression of hepatitis B virus X (HBx) gene is up-regulated by adriamycin at the post-transcriptional level
C Yun, JH Lee, JH Wang, JK Seong, SH Oh, DY Yu, H Cho |
Biochemical and Biophysical Research Communications | 2002 |
Hepatocarcinogenesis in hepatitis viral infection: lessons from transgenic mouse studies
K Koike |
Journal of Gastroenterology | 2002 |
Hepatitis Viruses
JH Ou |
2002 | |
Altered DNA Mutation Spectrum in Aflatoxin B1-Treated Transgenic Mice That Express the Hepatitis B Virus X Protein
CR Madden, MJ Finegold, BL Slagle |
Journal of virology | 2002 |
Hepatocarcinogenesis in hepatitis viral infection: lessons from transgenic mouse studies.
Koike K |
Journal of Gastroenterology | 2002 |
Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo
R Nijhara, SS Jana, SK Goswami, A Rana, SS Majumdar, V Kumar, DP Sarkar |
Journal of virology | 2001 |
X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis
J Diao, R Garces, CD Richardson |
Cytokine & Growth Factor Reviews | 2001 |
Role of hepatitis viruses in multistep hepatocarcinogenesis
K Koike |
Digestive and Liver Disease | 2001 |
Hepatitis B Virus X Protein Interferes with Cell Viability through Interaction with the p127-kDa UV-Damaged DNA-Binding Protein
N Lin-Marq, S Bontron, O Leupin, M Strubin |
Virology | 2001 |
Hepatitis B Virus X Protein Differentially Activates RAS-RAF-MAPK and JNK Pathways in X-transforming Versus Non-transforming AML12 Hepatocytes
C Tarn, S Lee, Y Hu, C Ashendel, OM Andrisani |
The Journal of biological chemistry | 2001 |
The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner
E Lara-Pezzi, S Roche, OM Andrisani, F Sánchez-Madrid, M López-Cabrera |
Oncogene | 2001 |
Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis
YC Kim, KS Song, G Yoon, MJ Nam, WS Ryu |
Oncogene | 2001 |
Hepatitis B Virus X Protein Acts as a Tumor Promoter in Development of Diethylnitrosamine-Induced Preneoplastic Lesions
CR Madden, MJ Finegold, BL Slagle |
Journal of virology | 2001 |
Hepatitis B Virus HBx Protein Activation of Cyclin A–Cyclin-Dependent Kinase 2 Complexes and G 1 Transit via a Src Kinase Pathway
M Bouchard, S Giannakopoulos, EH Wang, N Tanese, RJ Schneider |
Journal of virology | 2001 |
Role of NF-κB and Myc Proteins in Apoptosis Induced by Hepatitis B Virus HBx Protein
F Su, CN Theodosis, RJ Schneider |
Journal of virology | 2001 |
Microinjection Technique Used to Study Functional Interaction Between p53 and Hepatitis B Virus X Gene in Apoptosis
XW Wang |
Molecular Biotechnology | 2001 |
Expression of hepatitis B virus X protein does not alter the accumulation of spontaneous mutations in transgenic mice
CR Madden, MJ Finegold, BL Slagle |
Journal of virology | 2000 |
Different regions of hepatitis B virus X protein are required for enhancement of bZip-mediated transactivation versus transrepression
S Barnabas, OM Andrisani |
Journal of virology | 2000 |
Selective Transcriptional Regulations in the Human Liver Cell by Hepatitis B Viral X Protein
J Han, HY Yoo, BH Choi, HM Rho |
Biochemical and Biophysical Research Communications | 2000 |
The role of hepatitis B virus × gene in development of primary hepatocellular carcinoma
X Tao, D Shen, H Ren, X Zhang, D Zhang, B Gu, J Ye |
Science in China Series C: Life Sciences | 2000 |
Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)
C Bréchot, D Gozuacik, Y Murakami, P Paterlini-Bréchot |
Seminars in Cancer Biology | 2000 |
Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis
M Chami, D Gozuacik, K Saigo, T Capiod, P Falson, H Lecoeur, T Urashima, J Beckmann, ML Gougeon, M Claret, M Maire, C Bréchot, P Paterlini-Bréchot |
Oncogene | 2000 |
Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-β-induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway
WL Shih, ML Kuo, SE Chuang, AL Cheng, SL Doong |
The Journal of biological chemistry | 2000 |
Progress in Anti-Cancer Chemotherapy
D Khayat, GN Hortobagyi |
2000 | |
Hepatitis B Virus X Protein Activates Transcription by Bypassing CREB Phosphorylation, Not by Stabilizing bZIP−DNA Complexes
MK Pflum, TL Schneider, D Hall, A Schepartz |
Biochemistry | 2000 |
Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential
Z Rahmani, KW Huh, R Lasher, A Siddiqui |
Journal of virology | 2000 |
Hepatitis B virus in hepatocarcinogenesis
MA Feitelson |
Journal of Cellular Physiology | 1999 |
HIV and the New Viruses
S McAdam, F Gotch |
HIV and the New Viruses | 1999 |
Induction of apoptosis after switch-on of the hepatitis B virus X gene mediated by the Cre/loxP recombination system
S Kimura, Y Shintani, H Fujie, K Moriya, Y Kanegae, H Yotsuyanagi, I Saito, K Koike, T Tsutsumi |
Journal of General Virology | 1999 |
Differential Immediate Early Gene Expression in Conditional Hepatitis B Virus pX-transforming Versus Nontransforming Hepatocyte Cell Lines
C Tarn, ML Bilodeau, RL Hullinger, OM Andrisani |
The Journal of biological chemistry | 1999 |
Hepatitis B virus X mutants, present in hepatocellular carcinoma tissue abrogate both the antiproliferative and transactivation effects of HBx
H Sirma, C Giannini, K Poussin, P Paterlini, D Kremsdorf, C Bréchot |
Oncogene | 1999 |
The translation initiation factor, hu-Sui1 may be a target of hepatitis B X antigen in hepatocarcinogenesis
Z Lian, J Pan, J Liu, SM Zhang, M Zhu, P Arbuthnot, M Kew, MA Feitelson |
Oncogene | 1999 |
Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas
K Poussin, H Dienes, H Sirma, S Urban, M Beaugrand, D Franco, P Schirmacher, C Brchot, PP Brchot |
International Journal of Cancer | 1999 |
Regulation of RNA polymerase I-dependent promoters by the hepatitis B virus X protein via activated Ras and TATA-binding protein
HD Wang, A Trivedi, DL Johnson |
Molecular and cellular biology | 1998 |
Compensatory apoptosis in preneoplastic liver of a transgenic mouse model for viral hepatocarcinogenesis
K Koike, K Moriya, H Yotsuyanagi, Y Shintani, H Fujie, T Tsutsumi, S Kimura |
Cancer Letters | 1998 |
Identification of a protein isolated from senescent human cells that binds to hepatitis B virus X antigen
BS Sun, X Zhu, MM Clayton, J Pan, MA Feitelson |
Hepatology | 1998 |
Hepatitis B x Protein Inhibits p53-dependent DNA Repair in Primary Mouse Hepatocytes
S Prost, JM Ford, C Taylor, J Doig, DJ Harrison |
The Journal of biological chemistry | 1998 |
Hepatitis B virus X protein induces RNA polymerase III-dependent gene transcription and increases cellular TATA-binding protein by activating the Ras signaling pathway
HD Wang, A Trivedi, DL Johnson |
Molecular and cellular biology | 1997 |
Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras
NP Klein, RJ Schneider |
Molecular and cellular biology | 1997 |
The hepatitis B virus X gene induces p53-mediated programmed cell death
P Chirillo, S Pagano, G Natoli, PL Puri, VL Burgio, C Balsano, M Levrero |
Proceedings of the National Academy of Sciences | 1997 |
Hepatitis B virus X antigen in the pathogenesis of chronic infections and the development of hepatocellular carcinoma
MA Feitelson, LX Duan |
The American Journal of Pathology | 1997 |
Hepatitis B virus HBx protein activates transcription factor NF-kappaB by acting on multiple cytoplasmic inhibitors of rel-related proteins
F Su, RJ Schneider |
Journal of virology | 1996 |
Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathway
P Chirillo, M Falco, PL Puri, M Artini, C Balsano, M Levrero, G Natoli |
Journal of virology | 1996 |
Hepadnaviral X protein: Review of recent progress
TS Yen |
Journal of Biomedical Science | 1996 |
Hepatitis B virus-induced hepatocellular carcinoma: possible roles for HBx
JA Cromlish |
Trends in Microbiology | 1996 |
Hepatitis B and C viruses and primary liver cancer
C Brechot |
Bailliere's Clinical Gastroenterology | 1996 |
Interactions Between Alcohol and Hepatitis Viruses in the Liver
C Brechot, B Nalpas, MA Feitelson |
Clinics in Laboratory Medicine | 1996 |
Antiviral therapy of hepatitis B virus infection: Blocking viral gene expression
HE Blum, F Weizsäcker, S Wieland, S Offensperger, WB Offensperger |
Advanced Drug Delivery Reviews | 1995 |
Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls
J Benn, RJ Schneider |
Proceedings of the National Academy of Sciences | 1995 |
Metal Toxicology
E Foulkes |
Metal Toxicology | 1995 |
Advances in Virus Research
LA Babiuk, MJ Lawman, HB Ohmann |
Advances in virus research | 1988 |