Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease

Cancer Letters

Volumn 286, Issue 1, 2009, Pages 69-79

  Feitelson, Mark A ^a   Reis, Helena M G P V ^b   Lale Tufan, N ^c   Sun, Bill ^a   Pan, Jingbo ^d   Lian, Zhaorui ^a  

^a Temple University   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c PAMUKKALE UNIVERSITY   (Turkey)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Chronic liver disease; Cytokines; Hepatitis B virus; Hepatitis B x antigen; Transforming growth factor beta 1

Indexed keywords

BETA CATENIN; CASPASE; CYTOKINE; DNA FRAGMENT; FAS ANTIGEN; FIBRONECTIN; HEPATITIS B ANTIGEN; HEPATITIS B X ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MATRIX METALLOPROTEINASE; PHOSPHATIDYLINOSITOL 3 KINASE; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VIRUS DNA;

APOPTOSIS; CANCER GROWTH; CELL REGENERATION; CHRONIC LIVER DISEASE; DISEASE COURSE; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; FIBROGENESIS; GENE EXPRESSION; GENE FUNCTION; GENE REPLICATION; HEPATITIS B VIRUS; HUMAN; INFECTION; LIVER CARCINOGENESIS; LIVER CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; METASTASIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; SHORT SURVEY; SIGNAL TRANSDUCTION; VIRUS GENE;

HEPATITIS B VIRUS;

EID: 70350136670     PISSN: 03043835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.canlet.2008.12.010     Document Type: Review

References (122)

1. Beasley R.P., Hwang L.Y., Lin C.C., and Chien C.S. Hepatocellular carcinoma and HBV. A prospective study of 22,707 men in Taiwan. Lancet 2 (1981) 1129-1133
2. Beasley R.P., and Hwang L.Y. Epidemiology of hepatocellular carcinoma. In: Vyas G.N., Dienstag J.L., and Hoofnagle J.H. (Eds). Viral Hepatitis and Liver Disease (1984), Grune and Stratton Inc., New York 209-224
3. Chisari F.V., and Ferrari C. Hepatitis B virus immunopathology. Springer Semin. Immunopathol. 17 (1995) 261-281
4. Chisari F.V., and Ferrari C. Hepatitis B virus immunopathogenesis. Annu. Rev. Immunol. 13 (1995) 29-60
5. Liaw Y.F. Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy. Antivir. Ther. 11 (2006) 669-679
6. Chen C.J., Yang H.I., Su J., Jen C.L., You S.L., and Lu S.N. REVEAL-HBV study group, risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295 (2006) 65-73
7. Hui A.Y., and Friedman S.L. Molecular basis of hepatic fibrosis. Expert Rev. Mol. Med. 5 (2003) 1-23
8. Moreira R.K. Hepatic stellate cells and liver fibrosis. Arch. Pathol. Lab. Med. 131 (2007) 1728-1734
9. Sadek A.G., Mitchell D.G., Siegelman E.S., Outwater E.K., Matteucci T., and Hann H.W. Early hepatocellular carcinoma that develops within macroregenerative nodules: growth rate depicted at serial MR imaging. Radiology 195 (1995) 753-756
10. Mitchell D.G., Rubin R., Siegelman E.S., Burk Jr. D.L., and Rifkin M.D. Hepatocellular carcinoma within siderotic regenerative nodules: appearance as a nodule within a nodule on MR images. Radiology 178 (1991) 101-103
11. 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
12. 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
13. Hoofnagle J.H., Shafritz D.A., and Popper H. Chronic type B hepatitis and the "healthy" HBsAg carrier state. Hepatology 7 (1987) 758-763
14. Jin Y.M., Yun C., Park C., Wang H.J., and Cho H. Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases. J. Viral Hepat. 8 (2001) 322-330
15. Kim W.H., Hong F., Jaruga B., Zhang S.S., Fan S.J., Liang T.J., and Gao B. Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induce apoptosis by a caspase-3-dependent mechanism. Cell. Mol. Immunol. 2 (2005) 40-48
16. t: activation of NF-κB selective inhibition by antioxidants and integral membrane localization. EMBO J. 11 (1992) 2991-3001
17. Ohno H., Kaneko S., Kobayashi K., and Murakami S. Human hepatitis B virus enhancer 1 is responsive to human interleukin-6. J. Med. Virol. 52 (1997) 413-418
18. M.A. Feitelson, H.M.G.P.V. Reis, L.S. Tufan, J. Liu, M. Zhu, J. Pan, Z. Lian, Hepatitis B x antigen interference with tumor suppressor pathways in hepatocarcinognesis, in: J. Kobarg (Ed.), The Pleiotropic Functions of the Viral Protein HBx in HBV Infection and the Development of Liver Cancer. Research Signpost, Kerala, India, in press.
19. M.A. Feitelson, H.M.G.P.V. Reis, J. Liu, Z. Lian, J. Pan, Hepatitis B virus X antigen (HBxAg) and cell cycle control in chronic infection and hepatocarcinogenesis, in: R. Zhao (Ed.), Frontiers in Bioscience. Viral Infection and Cell Cycle Control, vol. 10, 2005, pp. 1558-1572.
20. Kim C.M., Koike K., Saito I., Miyamura T., and Jay G. HBx gene of HBV induces liver cancer in transgenic mice. Nature 351 (1991) 317-320
21. Koike K., Moriya K., Iino S., Yotsuyanagi H., Endo Y., Miyamura T., and Kurokawa K. High level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology 19 (1994) 810-819
22. Popper H., Roth L., Purcell R.H., Tennant B.C., and L Gerin J. Hepatocarcinogenicity of the woodchuck hepatitis virus. Proc. Natl. Acad. Sci. USA 84 (1987) 866-870
23. Chen H.S., Kaneko 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
24. 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
25. Matsubara K., and Tokino T. Integration of HBV DNA and its implications for hepatocarcinogenesis. Mol. Biol. Med. 7 (1990) 243-260
26. 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
27. Dejean A., Sonigo P., Wain-Hobson S., and Tiollais P. Specific hepatitis B virus integration in hepatocellular carcinoma DNA through a viral 11-base-pair direct repeat. Proc. Natl. Acad. Sci. USA 81 (1984) 5350-5354
28. Poussin K., Kienes H., Sirma H., Urban S., Beaugrand M., Franco D., et al. Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas. Int. J. Cancer 80 (1999) 497-505
29. Chen J.Y., Harrison T.J., Lee C.S., Chen D.S., and Zuckerman A.J. Detection of hepatitis B virus DNA in hepatocellular carcinoma: analysis by hybridization with subgenomic DNA fragments. Hepatology 8 (1988) 518-523
30. 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
31. Wang J., Chenivesse X., Henglein B., and Brechot C. Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343 (1990) 555-557
32. Feitelson M.A., and Lee J.M. Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis. Cancer Lett. 252 (2007) 157-170
33. Diamantis I.D., McGandy C.E., Chen T.J., Liaw Y.F., Gudat F., and Bianchi L. Hepatitis B X-gene expression in hepatocellar carcinoma. J. Hepatol. 15 (1992) 400-403
34. Paterlini P., Poussin K., Kew M., Franco D., and Brechot C. Selective accumulation of the X transcript of HBV in patients negative for HBsAg with HCC. Hepatology 21 (1995) 313-321
35. Hohne M., Schaefer S., Seifer M., Feitelson M.A., Paul D., and Gerlich W.G. Malignant transformation of immortalized hepatocytes by HBV DNA. EMBO J. 9 (1990) 1137-1145
36. Seifer M., Hohne M., Schaefer S., and Gerlich W.H. In vitro tumorigenicity of hepatitis B virus DNA and HBx protein. J. Hepatol. 13 Suppl 4 (1991) S61-S65
37. Wang W., London W.T., Lega L., and Feitelson M.A. HBxAg in liver from carrier patients with chronic hepatitis and cirrhosis. Hepatology 14 (1991) 29-37
38. Wang W., London W.T., and Feitelson M.A. HBxAg in HBV carrier patients with liver cancer. Cancer Res. 51 (1991) 4971-4977
39. Feitelson M.A., and Duan L.X. Hepatitis B virus x antigen in the pathogenesis of chronic infections and the development of hepatocellular carcinoma. Am. J. Pathol. 150 (1997) 1141-1157
40. Henkler F., and Koshy R. Hepatitis B virus transcriptional activators: mechanisms and possible role in oncogenesis. J. Viral Hepat. 3 (1996) 109-121
41. Takada S., and Koike K. Trans-activation function of a 3′ truncated X gene-cell fusion product from integrated HBV DNA in chronic hepatitis tissues. Proc. Natl. Acad. Sci. USA 87 (1990) 5628-5632
42. Wollersheim M., Debelka U., and Hofschneider P.H. A transactivating function encoded in the hepatitis B virus X gene is conserved in the integrated state. Oncogene 3 (1988) 545-552
43. Ou D.P., Tao Y.M., Tang F.Q., and Yang L.Y. The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by up-regulation of matrix metalloproteinases. Intl. J. Cancer 120 (2007) 1208-1214
44. Ou D.P., Tao Y.M., Chang Z.G., Tang F.Q., and Yang L.Y. Hepatocellular carcinoma cells containing hepatitis B virus X protein have enhanced invasive potential conditionally. Digest. Liver Dis. 38 (2006) 262-267
45. Tilg H., Kaser A., and Moschen A.R. How to modulate inflammatory cytokines in liver diseases. Liver Intl. 26 (2006) 1029-1039
46. Takehara T., Hayashi N., Katayama K., Kasahara A., Fusamoto H., Kato M., et al. Two-dimensional flow cytometric analysis of intrahepatic lymphocyte subsets from patients with chronic hepatitis. Dig. Dis. Sci. 36 (1991) 87-91
47. Mondelli M., Mieli-Vergani G., Bortolotti F., Cadrobbi P., Rortmann B., Alberti A., et al. Different mechanisms responsible for in vitro cell mediated cytotoxicity to autologous hepatocytes in children with autoimmune and HBsAg-positive chronic liver disease. J. Pediatr. 106 (1985) 899-906
48. Kagi D., Vignauz F., Ledermann B., Burki K., Depraetere V., Nagata S., et al. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265 (1994) 528-530
49. Hodgson P.D., Grant M.D., and Michalak T.I. Perforin and Fas/Fas ligand-mediated cytotoxicity in acute and chronic woodchuck viral hepatitis. Clin. Exp. Immunol. 118 (1999) 63-70
50. Nakamoto Y., Guidotti L.G., Pasquetto V., Schreiber R.D., and Chisari F.V. Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice. J. Immunol. 158 (1999) 5692-5697
51. Park Y.N., Chae K.J., Kim Y.B., Park C., and Theise N. Apoptosis and proliferation in hepatocarcinogenesis related to cirrhosis. Cancer 92 (2001) 2733-2736
52. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., et al. Lethal effects of the anti-Fas antibody in mice. Nature 364 (1993) 806-809
53. Ni R., Matsuda Y.TomitaK., Ichihara A., Ishimura K., Ogasawara J., et al. Fas-mediated apoptosis in primary cultured mouse hepatocytes. Exp. Cell Res. 215 (1994) 332-337
54. Luo K.X., Zhu Y.F., Zhang L.X., He H.T., Wang X.S., and Zhang L. In situ investigation of Fas/FasL expression in chronic hepatitis B infection and related liver diseases. J. Viral Hepat. 4 (1997) 303-307
55. Roskams T., Libbrecht L., van Dame B., and Desmet V. Fas and Fas ligand: strong co-expression in human hepatocytes surrounding hepatocellular carcinoma; can cancer induce suicide in peritumoral cells?. J. Pathol. 191 (2000) 150-153
56. Shin E.C., Shin J.S., Park J.H., and Kim S.J. Expression of Fas ligand in human hepatoma cell lines: role of hepatitis B virus X (HBX) in induction of Fas ligand. Int. J. Cancer 82 (1999) 587-591
57. Hayashi N., and Mita E. Involvement of Fas system-mediated apoptosis in pathogenesis of viral hepatitis. J. Viral Hepat. 6 (1999) 357-365
58. Chinnaiyan A.M., O'Rourke K., Tewari M., and Dixit V.M. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81 (1995) 505-512
59. Muzio M., Chinnaiyan A.M., Kischkel F.C., O'Rourke K., Shevchenk A., Ni J., et al. FLICE, a novel FADD-homologous ICE/CED 3-like protease, is recruited to the CD95 (Fas/APO-1) death inducing signaling complex. Cell 85 (1996) 817-827
60. Gupta S. Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci. 69 (2001) 2957-2964
61. Li H., Zhu H., Xu C.J., and Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94 (1998) 491-501
62. Roy S., and Nicholson D.W. Cross-talk in cell death signaling. J. Exp. Med. 192 (2000) F21-F25
63. Chen G.G., Lai P.B.S., Chak E.C.W., Xu H., Lee K.M., and Lau W.Y. Immunohistochemical analysis of proapoptotic Bid levels in chronic hepatitis, hepatocellular carcinoma and liver metastases. Cancer Lett. 172 (2001) 75-82
64. Chen G.G., Lai P.B.S., Chan P.K.S., Chak E.C.W., Yip J.H.Y., Ho R.L.K., et al. Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein. Eur. J. Cancer 37 (2001) 1695-1702
65. Pan J., Duan L.X., Sun B.S., and Feitelson M.A. Hepatitis B virus X protein decreases the anti-Fas induced apoptosis in human liver cells by inducing NF-κB. J. Gen. Virol. 82 Part 1 (2001) 171-182
66. Pan J., Lian Z., Wallett S., and Feitelson M.A. The hepatitis B x antigen effector, URG7, blocks tumor necrosis factor alpha mediated apoptosis by activation of phosphoinositol 3-kinase and β-catenin. J. Gen. Virol. 88 (2007) 3275-3285
67. Gottlob K., Fulco M., Levrero M., and Greessmann A. The hepatitis B virus HBx protein inhibits caspase 3 activity. J. Biol. Chem. 273 (1998) 33347-33353
68. Shih W.L., Kuo M.L., Chuang S.E., Cheng A.L., and Doong S.L. Hepatitis B virus X protein inhibits transforming growth factor-beta-induced apoptosis through the activation of phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 275 (2000) 25858-25864
69. Fang J.W., Shen W.W., Meager A., and Lau J.Y. Activation of the tumor necrosis factor alpha system in the liver in chronic hepatitis B virus infection. Am. J. Gastroenterol. 91 (1996) 748-753
70. Gonzalez-Amaro R., Garcia-Monzon C., Garcia-Buey L., Moreno-Otero R., Alonso J.L., Yague E., et al. Induction of tumor necrosis factor α production by human hepatocytes in chronic viral hepatitis. J. Exp. Med. 179 (1994) 841-848
71. Guang L.X. Hepatitis B virus infection in monocytes and their functional changes in patients with chronic hepatitis B. Chin. Med. J. 72 (1992) 651-654
72. Lara-Pezzi E., Majano P.L., Gomez-Gonzalo M., Garcia-Monzon C., Moreno-Otero R., Levrero M., et al. The hepatitis B virus X protein up-regulates tumor necrosis factor α gene expression in hepatocytes. Hepatology 28 (1998) 1013-1021
73. Kim W.H., Hong F., Jaruga B., Hu Z., Fan S., Liang T.J., et al. Additive activation of hepatic NF-κB by ethanol and HBx or HCV core protein: involvement of TNF-α receptor 1-independent and - dependent mechanisms. FASEB J. 15 (2001) 2551-2553
74. Soussan P., Garreau F., Zylberberg A., 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
75. Soussan P., Tuveri R., Nalpas B., Garreau F., Zavala F., Masson A., et al. The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis. J. Hepatol. 38 (2003) 343-348
76. Kandemir O., Polat G., Sahin E., Bagdatoglu O., Camdeviren H., and Kaya A. Fibronectin levels in chronic viral hepatitis and response of this protein to interferon therapy. Hepato-Gastroenterol. 51 (2004) 811-814
77. Budkowska A., Bedossa P., Groh F., Louise A., and Pillot J. Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain. J. Virol. 69 (1995) 840-848
78. Norton P.A., Reis M.G.P.V., and Feitelson M.A. Activation of fibronection gene expression by hepatitis B virus X antigen. J. Viral Hepat. 11 (2004) 332-341
79. Lara-Pezzi E., Majano P.L., Yanez-Mo M., Gomez-Gonzalo M., Carretero M., Moreno-Otero R., et al. Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix. J. Hepatol. 34 (2001) 409-415
80. Varner J.A., Emerson D.A., and Juliano R.L. Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by attachment to fibronectin. Mol. Biol. Cell 6 (1995) 725-740
81. Klein N.P., and Schneider R.J. Activation of src family kinases by hepatitis B virus HBx protein and coupled signaling to ras. Mol. Cell Biol. 17 (1997) 6427-6436
82. Lara-Pezzi E., Roche S., Andrisani O.M., Sanchez-Madrid F., and Lopez-Cabrera M. The hepatitis B virus protein induces adherens junction disruption in a src-dependent manner. Oncogene 20 (2001) 3323-3331
83. Myullyla R., Wang C., Keikkinen J., Juffer A., Lampela O., Risteli M., et al. Expanding the lysyl hydroxylase toolbox: new insights into the localization and activities of lysyl hydroxylase 3 (LH3). J. Cell. Physiol. 212 (2007) 323-329
84. Salo A.M., Wang C., Sipila L., Sormunen R., Vapola M., Kervinen P., et al. Lysyl hydroxylase 3 (LH3) modifies proteins in the extracellular space, a novel mechanism for matrix remodeling. J. Cell. Physiol. 207 (2006) 644-653
85. Castilla A., Prieto J., and Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alpha therapy. New Engl. J. Med. 324 (1991) 933-940
86. Liu F., Li B., and Nan Y. The effect of serum TGFβ1 of patients with chronic hepatitis B in liver fibrosis. Chin. J. Hepatol. 7 (1999) 196-198
87. Flisiak R., Al-Kadasi H., Jaroszewicz J., Prokopowicz .D., and Flisiak I. Effect of lamivudine treatment on plasma levels of transforming growth factor beta1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B. World J. Gastroenterol. 10 (2004) 2661-2665
88. Oshikawa O., Tamjura S., Kawata S., Ito N., Tsushima H., Kiso S., et al. The effect of hepatitis B virus X gene expression on response to growth inhibition by transforming growth factor beta 1. Biochem. Biophys. Res. Commun. 222 (1996) 770-773
89. Yoo Y.D., Ueda H., Park K., Flanders K.C., Lee Y.I., Jay G., et al. Regulation of transforming growth factor-beta 1 expression by the hepatitis B virus (HBV) X transactivator. Role in HBV pathogenesis. J .Clin. Invest. 97 (1996) 388-395
90. Pan J., Clayton M.M., and Feitelson M.A. HBxAg promotes transforming growth factor β1 (TGFβ1) activity by up-regulation of TGFβ1 and down-regulation of alpha 2-macroglobulin. J. Gen. Virol. 85 (2004) 275-282
91. Kakumu S., Ito Y., Takayanagi M., Yoshioka K., Wakita T., Ishikawa T., et al. Effect of recombinant human transforming growth factor beta 1 on immune responses in patients with chronic hepatitis B. Liver 13 (1993) 62-68
92. Ljumovic D., Diamantis I., Alegakis A.K., and Kouroumalis E.A. Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases. Clin. Chim. Acta 349 (2004) 203-211
93. Yu F.L., Liu H.J., Lee J.W., Liao M.H., and Shih W.L. Hepatitis B virus X protein promotes cell migration by inducing matrix metalloproteinase-3. J. Hepatol. 42 (2005) 520-527
94. Lara-Pezzi E., Gome-Gaviro M.V., Galvez B.G., Mira E., Iniguez M.A., Fresno M., et al. The hepatitis B virus X protein promotes tumor cells invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. J. Clin. Invest. 110 (2002) 1831-1838
95. Chung T.W., Lee Y.C., and Kim C.H. Hepatitis B viral HBx induces matrix metalloproteinase 9 gene expression through activation of ERKs and PI3K/AKT pathways: involvement of invasive potential. FASEB J. 18 (2004) 1123-1125
96. Chung T.W., Moon S.K., Lee Y.C., Kim J.G., Ko J.H., and Kim C.H. Enhanced expression of matrix metalloproteinase-9 by hepatitis B virus infection in liver cells. Arch. Biochem. Biophys. 408 (2002) 147-154
97. Kim J.R., and Kim C.H. Association of high activity of matrix metalloproteinase-9 to low levels of tissue inhibitors of metalloproteinase-1 and -3 in human hepatitis B - viral hepatoma cells. Int. J. Biochem. Cell Biol. 36 (2004) 2293-2306
98. Yin S.S., Li X.M., Wang B.E., Wang T.L., Jia J.D., and Qian L.X. The relationship of serum metalloproteinase with the severity of liver fibrosis and inflammation. Chin. J. Hepatol. 12 (2004) 666-668
99. Han Y.P. Matrix metalloproteinases, the pros and cons, in liver fibrosis. J. Gastroenterol. Hepatol. 21 (2006) S88-S91
100. Flisiak R., Maxwell P., Prokopowicz D., Timms P.M., and Panasiuk A. Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta-1: possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis. Hepato-Gastroenterol. 49 (2002) 1369-1372
101. Farrell G.C., and Teoh N.C. Management of chronic hepatitis B virus infection: a new era of disease control. Int. Med. J. 36 (2006) 100-113
102. Takehara T., Hayashi N., Mita E., Kanto T., Tatsumi T., Sasaki Y., et al. Delayed Fas-mediated hepatocytes apoptosis during liver regeneration in mice: hepatoprotective role of TNF alpha. Hepatology 27 (1998) 1643-1651
103. Lee Y., Park U.S., Choi I., Yoon S.K., Park Y.M., and Lee Y.I. Human interleukin 6 gene is activated by hepatitis B virus X protein in human hepatoma cells. Clin. Cancer Res. 4 (1998) 1711-1717
104. Diao J., Garces R., and Richardson C.D. X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. Cytokine Growth Factor Rev. 12 (2001) 189-205
105. Mahe Y., Mukaida N., Kuno K., Akiyama M., Ikeda N., Matsushima K., et al. Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. J. Biol. Chem. 266 (1991) 13759-13763
106. Sternlicht M.D., and Werb Z. How matrix metalloproteinases regulate cell behavior. Ann. Rev. Cell Dev. Biol. 17 (2001) 463-516
107. Lee M.O., Choi Y.H., Shin E.C., Kang H.J., Kim Y.M., Jeong S.Y., et al. Hepatitis B virus X protein induced expression of interleukin 18 (IL-18): a potential mechanism for liver injury caused by hepatitis B virus (HBV) infection. J. Hepatol. 37 (2002) 380-386
108. + human blood mononuclear cells. J. Clin. Invest. 101 (1998) 711-721
109. Tsutsui H., Nakanishi K., Matsui K., Higashino K., Okamura H., Miyazawa Y., et al. IFN-gamma-inducing factor up-regulates Fas ligands mediated cytotoxic activity of murine natural killer cell clones. J. Immunol. 157 (1996) 3967-3973
110. Dao T., Ohashi K., Kayano T., Kurimoto M., and Okamura H. Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell. Immunol. 173 (1996) 230-235
111. Yu D.Y., Moon H.B., Son J.K., Jeong S., Yu S.L., and Yoon H. Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X protein. J. Hepatol. 31 (1999) 123-132
112. Huang X., Yu C., Jin C., Kobayashi M., Bowles C.A., Wang F., et al. Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes accelerates hepatocarcinogenesis by driving proliferation and vascular endothelial growth factor-induced angiogenesis. Cancer Res. 66 (2006) 1481-1490
113. Qiu W.H., Zhou B.S., Chu P.G., Chen W.G., Chung C., Shih J., et al. Over-expression of fibroblast growth factor receptor 3 in human hepatocellular carcinoma. World J. Gastroenterol. 11 (2005) 5266-5272
114. Nicholes K., Guillet S., Tomlinson .E., Hillan K., Wright B., Frantz G.D., et al. A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice. Am. J. Pathol. 160 (2002) 2295-2307
115. Feng S.L., Guo Y., Factor V.M., Thorgeirsson S.S., Bell D.W., Testa J.R., et al. The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. Am. J. Pathol. 156 (2000) 1253-1261
116. Zhang B.B., Cai W.M., Weng H.L., Hu Z.R., Lu J., Zheng M., et al. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-beta1, matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis. World J. Gastroenterol. 9 (2003) 2490-2496
117. Lou S.M., Li Y.M., Wang K.M., Cai W.M., and Weng H.L. Expression of platelet-derived growth factor-BB in liver tissues of patients with chronic hepatitis B. World J. Gastroenterol. 10 (2004) 385-588
118. Campbell J.S., Hughes S.D., Gilbertson D.G., Palmer T.E., Holdren M.S., Haran A.C., et al. Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 102 (2005) 3389-3394
119. Martin-Vilchez S., Sanz-Cameno P., Rodriguez-Munoz Y., Majano P.L., Molina-Jimenez F., Lopez-Cabrera M., Moreno-Otero R., and Lara-Pezzi E. The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells. Hepatology 47 (2008) 1872-1883
120. Sanz-Cameno P., Martin-Vilchez S., Lara-Pezzi E., Borque M.J., Salmeron J., Munoz de Rueda P., Solis J.A., Lopez-Cabrera M., and Moreno-Otero R. Hepatitis B virus promotes angiopoietin-2 expression in liver tissue: role of HBV x protein. Am. J. Pathol. 169 (2006) 1215-1222
121. Gutierrez-Reyes G., Gutierrez-Ruiz M.C., and Kershenobich D. Liver fibrosis and chronic viral hepatitis. Arch. Med. Res. 38 (2007) 644-651
122. Akhurst R.J. TGF-beta antagonists: why suppress a tumor suppressor?. J. Clin. Invest. 109 (2002) 1533-1536