THE MOLECULAR MECHANISM OF HBx IN THE CARCINOGENESIS OF HEPATITIS B VIRUS RELATED HEPATOCELLULAR CARCINOMA_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Shaoqiang

Department of Hepato-Bilio-Surgery, The First Affiliated Hospital of Sun Yet-sen University of Medical Science, Guangzhou 510080;

Corresponding author：

Keywords：

HBx/HBV Hepatocellular carcinoma p53 protein Fas/CD95 gene

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To understand the molecular mechanism of HBx in the carcinogenesis of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC).
Methods The literatures published in the past 5 years which are mainly about HBx and hepatocellular carcinoma were reviewed.
Results HBx had many functions, such as cell malignant transformation, inhibiting DNA repair, trans-activation, inhibiting p53 and apoptosis. These functions together with its Fas/Fas-L interfering and caspase-3 inhibiting could contribute to the carcinogenesis and development of HBV relatde HCC.
Conclusion HBx has broad spectrum of biological functions, which contribute to the carcinogenesis and development of HBV related HCC.

Citation： LI Shaoqiang,LIANG Lijian.. THE MOLECULAR MECHANISM OF HBx IN THE CARCINOGENESIS OF HEPATITIS B VIRUS RELATED HEPATOCELLULAR CARCINOMA. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2001, 8(4): 279-281. doi: Copy

1.	Tabor E, Gerely RJ, Voegel CL, et al. Hepatitis B virus infection and primary hepatocellular carcinoma 〔Ｊ〕. J Natl Cancer Inst, 1977; 58(5)∶1197.
2.	Ritter SE, Whitten TM, Quets AT, et al. An internal domain of the hepatitis B virus X antigen is necessary for transactivating activity 〔Ｊ〕. Virology,1991; 182(2)∶841.
3.	Hohne M, Schaefer S, Feilson MA, et al. Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA 〔Ｊ〕. EMBO J, 1990; 9(2)∶1137.
4.	Becker SA, Lee TH, Butel JS, et al. Hepatitis B virusx protein interferes with cellular DNA repair 〔Ｊ〕. J Virol, 1998; 72(1)∶266.
5.	Qadri I, Ferrari ME, Siddiqui A. The hepatitis B virus transactivator protein, HBX, interacts with singlestranded DNA(ssDNA). Biochemical characterizations of the HBxssDNA interactions 〔Ｊ〕. J Biol Chem, 1996; 271(26)∶15443.
6.	Benn J, Su F, Doria M,et al. Hepatitis B virus protein induces transcription factor AP1 by activation of extracellular signalregulated and cJun Nterminal mitogenactivated protein kinases 〔Ｊ〕. J Virol, 1996; 70(8)∶4978.
7.	Benn J, Schneider RJ. Hepatitis B virus HBx protein activates RasGTP complex formation and establishes a Ras, Raf, MAP kinase signalling cascade 〔Ｊ〕. Proc Natl Acad USA, 1994; 91(22)∶10350.
8.	Su Q, Schoder CH, Hofmann WJ, et al. Expression of hepatitis B virus X protein in HBVinfected human livers and hepatocellular carcinoma 〔Ｊ〕. Hepatology, 1998; 27(4)∶1109.
9.	Nomura T, Lin Y, Dorjsuren D, et al. Human hepatitis B virus X protein is detectable in nuclei of transfected cells, and is active for transactivation 〔Ｊ〕. Biochim Biophys Acta, 1999; 1453(3)∶330.
10.	Koike K, Moriya K, Iino S, et al. Highlevel of expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice 〔Ｊ〕. Hepatology, 1994; 19(4)∶810.
11.	Leveillard T, Andera I, Bissonnette N, et al. Functional interactions between p53 and the TFIIH complex are affected by tumorassociated mutations 〔Ｊ〕. EMBO J, 1996; 15(7)∶1615.
12.	Wang XW, Gibson MK, Vermeulen W, et al. The XPB and XPD DNA helicases are components of the p53mediated apoptosis pathway 〔Ｊ〕. Genes Dev, 1996; 10(10)∶1219.
13.	Wu X, Levine AJ. p53 and E2 F1 cooperate to mediate apoptosis 〔Ｊ〕.Proc Natl Acaid Sci USA, 1994; 91(9)∶23602.
14.	Dulic V, Kaufmann WK, Wilson SJ, et al. p53dependent inhibition of cyclindependent kinase activities in human fibroblasts during radiationinduced G1 arrest 〔Ｊ〕. Cell, 1994; 76(6)∶1013.
15.	Harris C. p53: At the crossroads of molecular carcinogenesis and risk assessment 〔Ｊ〕. Science, 1993; 262(5142)∶1980.
16.	Oda T, Tsuda H, Scarpa A,et al. p53 gene mutation spectrum in hepatocellular carcinoma 〔Ｊ〕. Cancer Res, 1992; 52(22)∶6358.
17.	Greenblatt M, Bennett WP, Hollstein M, et al. Mutation in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis 〔Ｊ〕. Drug Metab Rev, 1994; 26(1-2)∶4855.
18.	Wang XW, Gibson MK, Vermeulen W, et al. Abrogation of p53induced apoptosis by the hepatitis B virus X gene 〔Ｊ〕. Cancer Res, 1995; 55(24)∶6012.
19.	Lin Y, Nomura T, Yamashita T, et al. The transactivation and p53interacting function of hepatitis B virus X protein are mutually interfering but distnct 〔Ｊ〕. Cancer Res, 1997; 57(22)∶5137.
20.	Wang XW, Forrester K, Yeh H, et al. Hepatitis B virus X protein inhibits p53 sequencespecific DNA binding, transcriptional activity, and association with transcription factor ERCC3 〔Ｊ〕. Proc Acad Sci USA, 1994; 91(6)∶2230.
21.	Elmore LW, Hancock AR, Chang SF, et al. Hepatitis B virus X protein and p53 tumor suppressor interaction in the modulation o apoptosis 〔Ｊ〕. Proc Acad Sci USA, 1997; 94(26)∶14707.
22.	Griffith TS, Ferguson TA. The role of FasLinduced apoptosis in immune privilege 〔Ｊ〕. Immunology Today, 1997; 18(5)∶240.
23.	Nagao M, Nakajima Y, Hisanaga M, et al. The alteration of Fas receptor and ligand system in hepatocellular carcinoma: How do hepatoma cells escape from the host immune surveillance in vivo 〔Ｊ〕? Hepatology, 1999; 30(2)∶413.
24.	Muller M, Wilder S, Bannasch D, et al. p53 activates CD95(APO1/Fas) gene in response to DNA damage by anticancer drugs 〔Ｊ〕. J Exp Med 1998; 188(11)∶2033.
25.	Shin EC, Shin JS, Park JH, et al . Expression of Fas ligand in human hepatoma cell lines: role of hepatitis B virus X (HBX) in induction of Fas ligand 〔Ｊ〕. Int J Cancer, 1999;82(4)∶587.
26.	Takada S, Kida M, Fukutomi H, et al . Interaction of hepatitis B virus X protein with a serine protease tryptase TL2 as an inhibitor 〔Ｊ〕. Oncogene, 1994; 9(2)∶341.
27.	Gottlob K, Fulco M, Levrero M, et al . The hepatitis B virus HBx protein inhibits capcase 3 activity 〔Ｊ〕. J Biol Chem, 1998; 273(50)∶33347.

1. Tabor E, Gerely RJ, Voegel CL, et al. Hepatitis B virus infection and primary hepatocellular carcinoma 〔Ｊ〕. J Natl Cancer Inst, 1977; 58(5)∶1197.
2. Ritter SE, Whitten TM, Quets AT, et al. An internal domain of the hepatitis B virus X antigen is necessary for transactivating activity 〔Ｊ〕. Virology,1991; 182(2)∶841.
3. Hohne M, Schaefer S, Feilson MA, et al. Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA 〔Ｊ〕. EMBO J, 1990; 9(2)∶1137.
4. Becker SA, Lee TH, Butel JS, et al. Hepatitis B virusx protein interferes with cellular DNA repair 〔Ｊ〕. J Virol, 1998; 72(1)∶266.
5. Qadri I, Ferrari ME, Siddiqui A. The hepatitis B virus transactivator protein, HBX, interacts with singlestranded DNA(ssDNA). Biochemical characterizations of the HBxssDNA interactions 〔Ｊ〕. J Biol Chem, 1996; 271(26)∶15443.
6. Benn J, Su F, Doria M,et al. Hepatitis B virus protein induces transcription factor AP1 by activation of extracellular signalregulated and cJun Nterminal mitogenactivated protein kinases 〔Ｊ〕. J Virol, 1996; 70(8)∶4978.
7. Benn J, Schneider RJ. Hepatitis B virus HBx protein activates RasGTP complex formation and establishes a Ras, Raf, MAP kinase signalling cascade 〔Ｊ〕. Proc Natl Acad USA, 1994; 91(22)∶10350.
8. Su Q, Schoder CH, Hofmann WJ, et al. Expression of hepatitis B virus X protein in HBVinfected human livers and hepatocellular carcinoma 〔Ｊ〕. Hepatology, 1998; 27(4)∶1109.
9. Nomura T, Lin Y, Dorjsuren D, et al. Human hepatitis B virus X protein is detectable in nuclei of transfected cells, and is active for transactivation 〔Ｊ〕. Biochim Biophys Acta, 1999; 1453(3)∶330.
10. Koike K, Moriya K, Iino S, et al. Highlevel of expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice 〔Ｊ〕. Hepatology, 1994; 19(4)∶810.
11. Leveillard T, Andera I, Bissonnette N, et al. Functional interactions between p53 and the TFIIH complex are affected by tumorassociated mutations 〔Ｊ〕. EMBO J, 1996; 15(7)∶1615.
12. Wang XW, Gibson MK, Vermeulen W, et al. The XPB and XPD DNA helicases are components of the p53mediated apoptosis pathway 〔Ｊ〕. Genes Dev, 1996; 10(10)∶1219.
13. Wu X, Levine AJ. p53 and E2 F1 cooperate to mediate apoptosis 〔Ｊ〕.Proc Natl Acaid Sci USA, 1994; 91(9)∶23602.
14. Dulic V, Kaufmann WK, Wilson SJ, et al. p53dependent inhibition of cyclindependent kinase activities in human fibroblasts during radiationinduced G1 arrest 〔Ｊ〕. Cell, 1994; 76(6)∶1013.
15. Harris C. p53: At the crossroads of molecular carcinogenesis and risk assessment 〔Ｊ〕. Science, 1993; 262(5142)∶1980.
16. Oda T, Tsuda H, Scarpa A,et al. p53 gene mutation spectrum in hepatocellular carcinoma 〔Ｊ〕. Cancer Res, 1992; 52(22)∶6358.
17. Greenblatt M, Bennett WP, Hollstein M, et al. Mutation in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis 〔Ｊ〕. Drug Metab Rev, 1994; 26(1-2)∶4855.
18. Wang XW, Gibson MK, Vermeulen W, et al. Abrogation of p53induced apoptosis by the hepatitis B virus X gene 〔Ｊ〕. Cancer Res, 1995; 55(24)∶6012.
19. Lin Y, Nomura T, Yamashita T, et al. The transactivation and p53interacting function of hepatitis B virus X protein are mutually interfering but distnct 〔Ｊ〕. Cancer Res, 1997; 57(22)∶5137.
20. Wang XW, Forrester K, Yeh H, et al. Hepatitis B virus X protein inhibits p53 sequencespecific DNA binding, transcriptional activity, and association with transcription factor ERCC3 〔Ｊ〕. Proc Acad Sci USA, 1994; 91(6)∶2230.
21. Elmore LW, Hancock AR, Chang SF, et al. Hepatitis B virus X protein and p53 tumor suppressor interaction in the modulation o apoptosis 〔Ｊ〕. Proc Acad Sci USA, 1997; 94(26)∶14707.
22. Griffith TS, Ferguson TA. The role of FasLinduced apoptosis in immune privilege 〔Ｊ〕. Immunology Today, 1997; 18(5)∶240.
23. Nagao M, Nakajima Y, Hisanaga M, et al. The alteration of Fas receptor and ligand system in hepatocellular carcinoma: How do hepatoma cells escape from the host immune surveillance in vivo 〔Ｊ〕? Hepatology, 1999; 30(2)∶413.
24. Muller M, Wilder S, Bannasch D, et al. p53 activates CD95(APO1/Fas) gene in response to DNA damage by anticancer drugs 〔Ｊ〕. J Exp Med 1998; 188(11)∶2033.
25. Shin EC, Shin JS, Park JH, et al . Expression of Fas ligand in human hepatoma cell lines: role of hepatitis B virus X (HBX) in induction of Fas ligand 〔Ｊ〕. Int J Cancer, 1999;82(4)∶587.
26. Takada S, Kida M, Fukutomi H, et al . Interaction of hepatitis B virus X protein with a serine protease tryptase TL2 as an inhibitor 〔Ｊ〕. Oncogene, 1994; 9(2)∶341.
27. Gottlob K, Fulco M, Levrero M, et al . The hepatitis B virus HBx protein inhibits capcase 3 activity 〔Ｊ〕. J Biol Chem, 1998; 273(50)∶33347.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

THE MOLECULAR MECHANISM OF HBx IN THE CARCINOGENESIS OF HEPATITIS B VIRUS RELATED HEPATOCELLULAR CARCINOMA

Abstract Full text Figures/Tables Video References Cited by

Format

Content