Mechanisms of HBV-related hepatocarcinogenesis

Journal of Hepatology

Volumn 52, Issue 4, 2010, Pages 594-604

  Neuveut, Christine ^a   Wei, Yu ^a   Buendia, Marie Annick ^a  

^a INSTITUT PASTEUR   (France)

Author keywords

Cancer; Hepatitis; Hepatocellular carcinoma; Oncogene; Tumour suppressor; Virus

Indexed keywords

ALANINE AMINOTRANSFERASE; BETA CATENIN; CYCLIN A; HEPATITIS B CORE ANTIGEN; HEPATITIS B VIRUS X PROTEIN; HEPATITIS B(E) ANTIGEN; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN P14; RAS PROTEIN; RETINOIC ACID RECEPTOR BETA; TRANSFORMING GROWTH FACTOR BETA; VIRUS DNA; WNT PROTEIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; CANCER RISK; CANCER SCREENING; DNA INTEGRATION; GENE EXPRESSION PROFILING; GENE MUTATION; GENOTYPE; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; LIFE CYCLE; LIVER CANCER; LIVER CARCINOGENESIS; LIVER FIBROSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; VIRUS REPLICATION;

CARCINOMA, HEPATOCELLULAR; GENES, TUMOR SUPPRESSOR; HEPATITIS B, CHRONIC; HUMANS; LIVER NEOPLASMS; ONCOGENES;

EID: 77949654113     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2009.10.033     Document Type: Review

References (146)

1. Ganem D., and Prince A.M. Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 350 (2004) 1118-1129
2. Zanetti A.R., Van Damme P., and Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine 26 (2008) 6266-6273
3. Parkin D.M. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118 (2006) 3030-3044
4. Hassan M.M., Hwang L.Y., Hatten C.J., Swaim M., Li D., Abbruzzese J.L., et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36 (2002) 1206-1213
5. Sun C.A., Wu D.M., Lin C.C., Lu S.N., You S.L., Wang L.Y., et al. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol 157 (2003) 674-682
6. Lee C.L., Hsieh K.S., and Ko Y.C. Trends in the incidence of hepatocellular carcinoma in boys and girls in Taiwan after large-scale hepatitis B vaccination. Cancer Epidemiol Biomarkers Prev 12 (2003) 57-59
7. Chen C.J., Yang H.I., Su J., Jen C.L., You S.L., Lu S.N., et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295 (2006) 65-73
8. Paterlini P., Driss F., Pisi E., Franco D., Berthelot P., and Bréchot C. Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg negative patients: a study of a low endemic area. Hepatology 17 (1993) 20-29
9. Pollicino T., Squadrito G., Cerenzia G., Cacciola I., Raffa G., Craxi A., et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 126 (2004) 102-110
10. Ikeda K., Kobayashi M., Someya T., Saitoh S., Hosaka T., Akuta N., et al. Occult hepatitis B virus infection increases hepatocellular carcinogenesis by eight times in patients with non-B, non-C liver cirrhosis: a cohort study. J Viral Hepat 16 (2009) 437-443
11. Ming L., Thorgeirsson S.S., Gail M.H., Lu P., Harris C.C., Wang N., et al. Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 36 (2002) 1214-1220
12. El-Serag H.B. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127 (2004) S27-S34
13. Bruix J., Boix L., Sala M., and Llovet J.M. Focus on hepatocellular carcinoma. Cancer Cell 5 (2004) 215-219
14. Bruix J., Hessheimer A.J., Forner A., Boix L., Vilana R., and Llovet J.M. New aspects of diagnosis and therapy of hepatocellular carcinoma. Oncogene 25 (2006) 3848-3856
15. Avila M.A., Berasain C., Sangro B., and Prieto J. New therapies for hepatocellular carcinoma. Oncogene 25 (2006) 3866-3884
16. Summers J., and Mason W.S. Replication of the genome of a hepatitis B - like virus by reverse transcription of an RNA intermediate. Cell 29 (1982) 403-415
17. Soussan P., Garreau F., Zylberberg H., Ferray C., Brechot C., and Kremsdorf D. In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA. J Clin Invest 105 (2000) 55-60
18. Breiner K.M., Schaller H., and Knolle P.A. Endothelial cell-mediated uptake of a hepatitis B virus: a new concept of liver targeting of hepatotropic microorganisms. Hepatology 34 (2001) 803-808
19. Rabe B., Vlachou A., Panté N., Helenius A., and Kann M. Nuclear import of hepatitis B virus capsids and release of the viral genome. Proc Natl Acad Sci USA 100 (2003) 9849-9854
20. Beck J., and Nassal M. Hepatitis B virus replication. World J Gastroenterol 13 (2007) 48-64
21. Mason W.S., Seal G., and Summers J. Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol 36 (1980) 829-836
22. Weiser B., Ganem D., Seeger C., and Varmus H.E. Closed circular viral DNA and asymmetrical heterogeneous forms in livers from animals infected with ground squirrel hepatitis virus. J Virol 48 (1983) 1-9
23. Tang H., Delgermaa L., Huang F., Oishi N., Liu L., He F., et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication. J Virol 79 (2005) 5548-5556
24. Bock C.T., Schranz P., Schroder C.H., and Zentgraf H. Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell. Virus Genes 8 (1994) 215-229
25. Lewin S., Walters T., and Locarnini S. Hepatitis B treatment: rational combination chemotherapy based on viral kinetic and animal model studies. Antiviral Res 55 (2002) 381-396
26. Pollicino T., Belloni L., Raffa G., Pediconi N., Squadrito G., Raimondo G., et al. Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones. Gastroenterology 130 (2006) 823-837
27. Chen H.S., Kanako S., Girones R., Anderson R.W., Hornbuckle W.E., Tennant B.C., et al. The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J Virol 67 (1993) 1218-1226
28. Zoulim F., Saputelli J., and Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 68 (1994) 2026-2030
29. Leupin O., Bontron S., Schaeffer C., and Strubin M. Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependent pathway distinct from that leading to cell death. J Virol 79 (2005) 4238-4245
30. Keasler V.V., Hodgson A.J., Madden C.R., and Slagle B.L. Enhancement of hepatitis B virus replication by the regulatory X protein in vitro and in vivo. J Virol 81 (2007) 2656-2662
31. Keasler V.V., Hodgson A.J., Madden C.R., and Slagle B.L. Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice. Virology 390 (2009) 122-129
32. Tuttleman J.S., Pourcel C., and Summers J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47 (1986) 451-460
33. Ganem D. Hepadnaviridae: the viruses and their replication. In: Fields B., Knipe D., and Howley P. (Eds). Fields virology (1996), Lippincott-Raven, Philadelphia 2703-2737
34. Wei Y., and Tiollais P. Molecular biology of hepatitis B virus. Clin Liver Dis 3 (1999) 189-219
35. Hoofnagle J.H., Doo E., Liang T.J., Fleischer R., and Lok A.S. Management of hepatitis B: summary of a clinical research workshop. Hepatology 45 (2007) 1056-1075
36. Liver EAftSot. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50 (2009) 227
37. Ikeda H, Sasakia M, Satoa Y, Haradaa K, Zenc Y, Mitsuid T, et al. Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion. Human Pathol, in press. doi: 10.1016/j.humpath.2009.1006.1009.
38. Collado M., Blasco M.A., and Serrano M. Cellular senescence in cancer and aging. Cell 130 (2007) 223-233
39. Realdi G., Alberti A., Rugge M., Bortolotti F., Rigoli A.M., Tremolada F., et al. Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology 79 (1980) 195-199
40. Liaw Y.F., Chu C.M., Su I.J., Huang M.J., Lin D.Y., and Chang-Chien C.S. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology 84 (1983) 216-219
41. Martinot-Peignoux M., Boyer N., Colombat M., Akremi R., Pham B.N., Ollivier S., et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol 36 (2002) 543-546
42. Carman W.F., Jacyna M.R., Hadziyannis S., Karayiannis P., McGarvey M.J., Markis A., et al. Mutation preventing formation of hepatitis e antigen in patients with chronic hepatitis B infection. Lancet ii (1989) 588-591
43. Paterlini P., Gerken G., Khemeny F., Franco D., D'Errico A., Grigioni W., et al. Primary liver cancer in HBsAg-negative patients: a study of HBV genome using the polymerase chain reaction. In: Hollinger F.B., Lemon S.M., and Margolis H. (Eds). Viral hepatitis and liver disease (1991), Williams and Wilkins, USA 605-610
44. Rehermann B., Ferrari C., Pasquinelli C., and Chisari F.V. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 2 (1996) 1104-1108
45. Fattovich G., Bortolotti F., and Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 48 (2008) 335-352
46. Honda M., Kaneko S., Kawai H., Shirota Y., and Kobayashi K. Differential gene expression between chronic hepatitis B and C hepatic lesion. Gastroenterology 120 (2001) 955-966
47. Honda M., Yamashita T., Ueda T., Takatori H., Nishino R., and Kaneko S. Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C. Hepatology 44 (2006) 1122-1138
48. Yuen M.F., Tanaka Y., Fong D.Y., Fung J., Wong D.K., Yuen J.C., et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 50 (2009) 80-88
49. Buendia M.A. Genetics of hepatocellular carcinoma. Semin Cancer Biol 10 (2000) 185-200
50. Laurent-Puig P., and Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene 25 (2006) 3778-3786
51. Lee J.S., and Thorgeirsson S.S. Comparative and integrative functional genomics of HCC. Oncogene 25 (2006) 3801-3809
52. de La Coste A., Romagnolo B., Billuart P., Renard C.A., Buendia M.A., Soubrane O., et al. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci USA 95 (1998) 8847-8851
53. Hussain S.P., Schwank J., Staib F., Wang X.W., and Harris C.C. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 26 (2007) 2166-2176
54. Villanueva A., Chiang D.Y., Newell P., Peix J., Thung S., Alsinet C., et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 135 (2008) 1972-1983
55. Breuhahn K., Longerich T., and Schirmacher P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 25 (2006) 3787-3800
56. Legoix P., Bluteau O., Bayer J., Perret C., Balabaud C., Belghiti J., et al. Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. Oncogene 18 (1999) 4044-4046
57. Laurent-Puig P., Legoix P., Bluteau O., Belghiti J., Franco D., Binot F., et al. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 120 (2001) 1763-1773
58. Cavard C., Colnot S., Audard V., Benhamouche S., Finzi L., Torre C., et al. Wnt/beta-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology. Future Oncol 4 (2008) 647-660
59. Audard V., Grimber G., Elie C., Radenen B., Audebourg A., Letourneur F., et al. Cholestasis is a marker for hepatocellular carcinomas displaying beta-catenin mutations. J Pathol 212 (2007) 345-352
60. Benhamouche S., Decaens T., Godard C., Chambrey R., Rickman D.S., Moinard C., et al. Apc tumor suppressor gene is the "zonation-keeper" of mouse liver. Dev Cell 10 (2006) 759-770
61. Hailfinger S., Jaworski M., Braeuning A., Buchmann A., and Schwarz M. Zonal gene expression in murine liver: lessons from tumors. Hepatology 43 (2006) 407-414
62. Boyault S., Rickman D.S., de Reynies A., Balabaud C., Rebouissou S., Jeannot E., et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 45 (2007) 42-52
63. Matsuzaki K. Modulation of TGF-beta signaling during progression of chronic liver diseases. Front Biosci 14 (2009) 2923-2934
64. Rossmanith W., and Schulte-Hermann R. Biology of transforming growth factor beta in hepatocarcinogenesis. Microsc Res Tech 52 (2001) 430-436
65. Fransvea E., Mazzocca A., Antonaci S., and Giannelli G. Targeting transforming growth factor (TGF)-betaRI inhibits activation of beta1 integrin and blocks vascular invasion in hepatocellular carcinoma. Hepatology 49 (2009) 839-850
66. Tanaka S., and Arii S. Molecularly targeted therapy for hepatocellular carcinoma. Cancer Sci 100 (2009) 1-8
67. Lee J.S., Heo J., Libbrecht L., Chu I.S., Kaposi-Novak P., Calvisi D.F., et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12 (2006) 410-416
68. Hsieh Y.H., Wu T.T., Huang C.Y., Hsieh Y.S., Hwang J.M., and Liu J.Y. p38 mitogen-activated protein kinase pathway is involved in protein kinase Calpha-regulated invasion in human hepatocellular carcinoma cells. Cancer Res 67 (2007) 4320-4327
69. Chen F., Beezhold K., and Castranova V. JNK1, a potential therapeutic target for hepatocellular carcinoma. Biochim Biophys Acta 1796 (2009) 242-251
70. Llovet J.M., and Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48 (2008) S20-S37
71. Newell P., Toffanin S., Villanueva A., Chiang D.Y., Minguez B., Cabellos L., et al. Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo. J Hepatol 51 (2009) 725-733
72. Staib F., Hussain S.P., Hofseth L.J., Wang X.W., and Harris C.C. TP53 and liver carcinogenesis. Hum Mutat 21 (2003) 201-216
73. Zucman-Rossi J., Benhamouche S., Godard C., Boyault S., Grimber G., Balabaud C., et al. Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas. Oncogene 26 (2007) 774-780
74. Calvisi D.F., Ladu S., Gorden A., Farina M., Conner E.A., Lee J.S., et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 130 (2006) 1117-1128
75. Pineau P., Marchio A., Nagamori S., Seki S., Tiollais P., and Dejean A. Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis. Hepatology 37 (2003) 852-861
76. Marchio A., Pineau P., Meddeb M., Terris B., Tiollais P., Bernheim A., et al. Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Oncogene 19 (2000) 3733-3738
77. Yamashita T., Forgues M., Wang W., Kim J.W., Ye Q., Jia H., et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68 (2008) 1451-1461
78. Hoshida Y., Nijman S.M., Kobayashi M., Chan J.A., Brunet J.P., Chiang D.Y., et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69 (2009) 7385-7392
79. Woo H.G., Park E.S., Cheon J.H., Kim J.H., Lee J.S., Park B.J., et al. Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma. Clin Cancer Res 14 (2008) 2056-2064
80. Liu S., Zhang H., Gu C., Yin J., He Y., Xie J., et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst 101 (2009) 1066-1082
81. Sumi H., Yokosuka O., Seki N., Arai M., Imazeki F., Kurihara T., et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 37 (2003) 19-26
82. Westland C., Delaney W., Yang H., Chen S.S., Marcellin P., Hadziyannis S., et al. Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil1. Gastroenterology 125 (2003) 107-116
83. Yotsuyanagi H., Hino K., Tomita E., Toyoda J., Yasuda K., and Iino S. Precore and core promoter mutations, hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B. J Hepatol 37 (2002) 355-363
84. Yang H.I., Lu S.N., Liaw Y.F., You S.L., Sun C.A., Wang L.Y., et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 347 (2002) 168-174
85. Kao J.H., Chen P.J., Lai M.Y., and Chen D.S. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 124 (2003) 327-334
86. Tanaka Y., Hasegawa I., Kato T., Orito E., Hirashima N., Acharya S.K., et al. A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D. Hepatology 40 (2004) 747-755
87. Orito E., and Mizokami M. Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Intervirology 46 (2003) 408-412
88. Ni Y.H., Chang M.H., Wang K.J., Hsu H.Y., Chen H.L., Kao J.H., et al. Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology 127 (2004) 1733-1738
89. Chan H.L., Wong M.L., Hui A.Y., Hung L.C., Chan F.K., and Sung J.J. Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigen-positive patients. J Clin Microbiol 41 (2003) 1277-1279
90. Chan H.L., Hui A.Y., Wong M.L., Tse A.M., Hung L.C., Wong V.W., et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 53 (2004) 1494-1498
91. Kuang S.Y., Jackson P.E., Wang J.B., Lu P.X., Munoz A., Qian G.S., et al. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc Natl Acad Sci USA 101 (2004) 3575-3580
92. Lugassy C., Bernuau J., Thiers V., Krosgaard K., Degott C., Wantzin P., et al. Sequences of hepatitis B virus DNA in the serum and liver of patients with acute benign and fulminant hepatitis. J Infect Dis 155 (1987) 64-71
93. Yaginuma K., Kobayashi H., Kobayashi M., Morishima T., Matsuyama K., and Koike K. Multiple integration site of hepatitis B virus DNA in hepatocellular carcinoma and chronic active hepatitis tissues from children. J Virol 61 (1987) 1808-1813
94. Boender P.J., Schalm S.W., and Heijtink R.A. Detection of integration during active replication of hepatitis B virus in the liver. J Med Virol 16 (1985) 47-54
95. Tanaka Y., Esumi M., and Shikata T. Frequent integration of hepatitis B virus DNA in noncancerous liver tissue from hepatocellular carcinoma patients. J Med Virol 26 (1988) 7-14
96. Bréchot C., Pourcel C., Louise A., Rain B., and Tiollais P. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature 286 (1980) 533-535
97. Brechot C., Gozuacik D., Murakami Y., and Paterlini-Brechot P. Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 10 (2000) 211-231
98. Tokino T., and Matsubara K. Chromosomal sites for hepatitis B virus integration in human hepatocellular carcinoma. J Virol 65 (1991) 6761-6764
99. Dejean A., Bougueleret L., Grzeschik K.H., and Tiollais P. Hepatitis B virus DNA integration in a sequence homologous to v-erbA and steroid receptor genes in a hepatocellular carcinoma. Nature 322 (1986) 70-72
100. De Thé H., Marchio A., Tiollais P., and Dejean A. A novel steroid/thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma. Nature 330 (1987) 667-670
101. Wang J., Chenivesse X., Henglein B., and Bréchot C. Hepatitis B virus integration in a cyclin A gene in a human hepatocellular carcinoma. Nature 343 (1990) 555-557
102. Wang J., Zindy F., Chenivesse X., Lamas E., Henglein B., and Brechot C. Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma. Oncogene 7 (1992) 1653-1656
103. Garcia M., de The H., Tiollais P., Samarut J., and Dejean A. A hepatitis B virus pre-S-retinoic acid receptor beta chimera transforms erythrocytic progenitor cells in vitro. Proc Natl Acad Sci USA 90 (1993) 89-93
104. Berasain C., Patil D., Perara E., Huang S.M., Mouly H., and Brechot C. Oncogenic activation of a human cyclin A2 targeted to the endoplasmic reticulum upon hepatitis B virus genome insertion. Oncogene 16 (1998) 1277-1288
105. Paterlini-Brechot P., Saigo K., Murakami Y., Chami M., Gozuacik D., Mugnier C., et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene 22 (2003) 3911-3916
106. Murakami Y., Saigo K., Takashima H., Minami M., Okanoue T., Brechot C., et al. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut 54 (2005) 1162-1168
107. Mikkers H., Allen J., Knipscheer P., Romeijn L., Hart A., Vink E., et al. High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. Nat Genet 32 (2002) 153-159
108. Wu X., Li Y., Crise B., and Burgess S.M. Transcription start regions in the human genome are favored targets for MLV integration. Science 300 (2003) 1749-1751
109. Horikawa I., and Barrett J.C. cis-Activation of the human telomerase gene (hTERT) by the hepatitis B virus genome. J Natl Cancer Inst 93 (2001) 1171-1173
110. Ferber M.J., Montoya D.P., Yu C., Aderca I., McGee A., Thorland E.C., et al. Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Oncogene 22 (2003) 3813-3820
111. Tamori A., Yamanishi Y., Kawashima S., Kanehisa M., Enomoto M., Tanaka H., et al. Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. Clin Cancer Res 11 (2005) 5821-5826
112. Yaginuma K., Kobayashi M., Yoshida E., and Koike K. Hepatitis B virus integration in hepatocellular carcinoma DNA: duplication of cellular flanking sequences at the integration site. Proc Natl Acad Sci USA 82 (1985) 4458-4462
113. Tokino T., Fukushige S., Nakamura T., Nagaya T., Murotsu T., Shiga K., et al. Chromosomal translocation and inverted duplication associated with integrated hepatitis B virus in hepatocellular carcinomas. J Virol 61 (1987) 3848-3854
114. Hino O., Shows T.B., and Rogler C.E. Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation. Proc Natl Acad Sci USA 83 (1986) 8338-8342
115. Hino O., Tabata S., and Hotta Y. Evidence for increased in vitro recombination with insertion of human hepatitis B virus DNA. Proc Natl Acad Sci USA 88 (1991) 9248-9252
116. Tsuei D.J., Chang M.H., Chen P.J., Hsu T.Y., and Ni Y.H. Characterization of integration patterns and flanking cellular sequences of hepatitis B virus in childhood hepatocellular carcinomas. J Med Virol 68 (2002) 513-521
117. Andrisani O.M., and Barnabas S. The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis (Review). Int J Oncol 15 (1999) 373-379
118. Bouchard M.J., and Schneider R.J. The enigmatic X gene of hepatitis B virus. J Virol 78 (2004) 12725-12734
119. Tang H., Oishi N., Kaneko S., and Murakami S. Molecular functions and biological roles of hepatitis B virus x protein. Cancer Sci 97 (2006) 977-983
120. Seifer M., Hohne M., Schaefer S., and Gerlich W.H. In vitro tumorigenicity of hepatitis B virus DNA and HBx protein. J Hepatol 13 (1991) S61-S65
121. Gottlob K., Pagano S., Levrero M., and Graessmann A. Hepatitis B virus X protein transcription activation domains are neither required nor sufficient for cell transformation. Cancer Res 58 (1998) 3566-3570
122. Kim Y.C., Song K.S., Yoon G., Nam M.J., and Ryu W.S. Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 20 (2001) 16-23
123. Oishi N., Shilagardi K., Nakamoto Y., Honda M., Kaneko S., and Murakami S. Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells. Cancer Sci 98 (2007) 1540-1548
124. Oguey D., Dumenco L.L., Pierce R.H., and Fausto N. Analysis of the tumorigenicity of the X gene of hepatitis B virus in a nontransformed hepatocyte cell line and the effects of cotransfection with a murine p53 mutant equivalent to human codon 249. Hepatology 24 (1996) 1024-1033
125. Schuster R., Gerlich W.H., and Schaefer S. Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts. Oncogene 19 (2000) 1173-1180
126. Su Q., Schrôder C.H., Hofman W.J., Otto G., Pichlmayr R., and Bannasch P. Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinoma. Hepatology 27 (1998) 1109-1120
127. Kim C.M., Koike K., Saito I., Miyamura T., and Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351 (1991) 317-320
128. Reifenberg K., Pudollek H.P., Schmitteckert E., Spindler G., Köck J., and Schlicht H.J. Long-term expression of hepatitis B virus core-e- and X-proteins does not cause pathologic changes in transgenic mice. J Hepatol 26 (1997) 119-130
129. Slagle B.L., Lee T.H., Medina D., Finegold M.J., and Butel J.S. Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus x gene. Mol Carcinog 15 (1996) 261-269
130. Terradillos O., Billet O., Renard C.A., Lévy R., Molina T., Briand P., et al. The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 14 (1997) 395-404
131. Terradillos O., Pollicino T., Lecoeur H., Tripodi M., Gougeon M.L., Tiollais P., et al. p53-independent apoptotic effects of the hepatitis B virus HBx protein in vivo and in vitro. Oncogene 17 (1998) 2115-2123
132. Madden C.R., Finegold M.J., and Slagle B.L. Hepatitis B virus X protein acts as a tumor promoter in development of diethylnitrosamine-induced preneoplastic lesions. J Virol 75 (2001) 3851-3858
133. Madden C.R., Finegold M.J., and Slagle B.L. Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. J Virol 76 (2002) 11770-11774
134. Wu B.K., Li C.C., Chen H.J., Chang J.L., Jeng K.S., Chou C.K., et al. Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis B virus X protein transgenic mice. Biochem Biophys Res Commun 340 (2006) 916-928
135. Tralhao J.G., Roudier J., Morosan S., Giannini C., Tu H., Goulenok C., et al. Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: an alternative mechanism of HBx-related pathogenesis. Proc Natl Acad Sci USA 99 (2002) 6991-6996
136. Hodgson A.J., Keasler V.V., and Slagle B.L. Premature cell cycle entry induced by hepatitis B virus regulatory HBx protein during compensatory liver regeneration. Cancer Res 68 (2008) 10341-10348
137. Rossner M.T. Hepatitis B virus X-gene product: a promiscuous transcriptional activator. J Med Virol 36 (1992) 101-117
138. Yen B.T.S. Hepadnaviral X protein: review of recent progress. J Biomed Sci 3 (1996) 20-30
139. Cougot D., Buendia M.A., and Neuveut C. Carcinogenesis induced by hepatitis B virus. In: Chan S.H.H. (Ed). Translational research in biomedecine (2008), Karger, Basel 108-136
140. Cougot D., Wu Y., Cairo S., Caramel J., Renard C.A., Levy L., et al. The hepatitis B virus X protein functionally interacts with CREB-binding protein/p300 in the regulation of CREB-mediated transcription. J Biol Chem 282 (2007) 4277-4287
141. Barnabas S., Hai T., and Andrisani O.M. The hepatitis B virus X protein enhances the DNA binding potential and transcription efficacy of bZip transcription factors. J Biol Chem 272 (1997) 20684-20690
142. Abramovitch R., Tavor E., Jacob-Hirsch J., Zeira E., Amariglio N., Pappo O., et al. A pivotal role of cyclic AMP-responsive element binding protein in tumor progression. Cancer Res 64 (2004) 1338-1346
143. Lehrmann H., Pritchard L.L., and Harel-Bellan A. Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation. Adv Cancer Res 86 (2002) 41-65
144. Kim S., Park S.Y., Yong H., Famulski J.K., Chae S., Lee J.H., et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. Oncogene 27 (2008) 3457-3464
145. Wen Y., Golubkov V.S., Strongin A.Y., Jiang W., and Reed J.C. Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation. J Biol Chem 283 (2008) 2793-2803
146. Rakotomalala L., Studach L., Wang W.H., Gregori G., Hullinger R.L., and Andrisani O. Hepatitis B virus X protein increases the Cdt1-to-geminin ratio inducing DNA re-replication and polyploidy. J Biol Chem 283 (2008) 28729-28740