Skip to main content
SpringerLink
Log in

Abrogation of p53-Induced Apoptosis by the Hepatitis B Virus X Gene

  • Protocol
Hepatocellular Carcinoma

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 45))

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has become a leading cause for cancer-related deaths in adults from Asia and sub-Saharan Africa (1). The DNA tumor virus hepatitis B virus (HBV) has been implicated to play a major causative role in the development of HCC in man (2–4). The HBx gene, the smallest viral openreading frame that may be essential for the viral life cycle (5,6), largely contributes the oncogenecity of HBV. The selective retention and expression of the HBx gene during acute and chronic hepatitis as well as in a great majority of HCCs may constitute an important step during HCC development (7,8). The oncogenic potential of the HBx gene has been experimentally demonstrated in a transgenic mice model (9) and in cell culture systems (10,11). HBx alone can induce HCC in certain transgenic mice (9) or can increase susceptibility to chemical carcinogens (12) and accelerate c-myc-induced HCC (13). Consequently, as an oncoprotein, HBx has been reported to disregulate cell-cycle transition (14,15) to potentially target certain proteases and proteasome (16–18), to interact with DNA repair factors (19,20), or to interact with the p53 tumor suppressor gene product (21–24).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Di Bisceglie, A. M., Rustgi, V. K., Hoofnagle, J. H., Dusheiko, G. M., and Lotze, M. T. (1988) NIH conference. Hepatocellular carcinoma. Ann. Intern. Med. 108, 390–401.

    PubMed  Google Scholar 

  2. Beasley, R. P., Hwang, L. Y., Lin, C. C., and Chien, C. S. (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 2, 1129–1133.

    Article  CAS  PubMed  Google Scholar 

  3. Popper, H., Shafritz, D. A., and Hoofnagle, J. H. (1987) Relation of the hepatitis B virus carrier state to hepatocellular carcinoma. Hepatology. 7, 764–772.

    Article  CAS  PubMed  Google Scholar 

  4. Beasley, R. P. (1988) Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer. 61, 1942–1956.

    Article  CAS  PubMed  Google Scholar 

  5. Chen, H. S., Kaneko, S., Girones, R., Anderson, R. W., Hornbuckle, W. E., Tennant, B. C., et al. (1993) The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J. Virol. 67, 1218–1226.

    CAS  PubMed  Google Scholar 

  6. Zoulim, F., Saputelli, J., and Seeger, C. (1994) Woodchuck hepatitis virus X protein is required for viral infection in vivo. J. Virol. 68, 2026–2030.

    CAS  PubMed  Google Scholar 

  7. Unsal, H., Yakicier, C., Marcais, C., Kew, M., Volkmann, M., Zentgraf, H., Isselbacher, K. J., and Ozturk, M. (1994) Genetic heterogeneity of hepatocellular carcinoma. Proc. Natl. Acad. Sci USA 91, 822–826.

    Article  CAS  PubMed  Google Scholar 

  8. Paterlini, P., Poussin, K., Kew, M., Franco, D., and Brechot, C. (1995) Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma. Hepatology. 21, 313–321.

    CAS  PubMed  Google Scholar 

  9. Kim, C. M., Koike, K., Saito, I., Miyamura, T., and Jay, G. (1991) HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 351, 317–320.

    Article  CAS  PubMed  Google Scholar 

  10. Shirakata, Y., Kawada, M., Fujiki, Y., Sano, H., Oda, M., Yaginuma, K., et al. (1989) The X gene of hepatitis B virus induced growth stimulation and tumorigenic transformation of mouse NIH3T3 cells. Jpn. J. Cancer Res. 80, 617–621.

    CAS  PubMed  Google Scholar 

  11. Hohne, M., Schaefer, S., Seifer, M., Feitelson, M. A., Paul, D., and Gerlich, W. H. (1990) Malignant transformation of immortalized transgenic hepatocytes after transfection with hepatitis B virus DNA. EMBO J. 9, 1137–1145.

    CAS  PubMed  Google Scholar 

  12. Slagle, B. L., Lee, T. H., Medina, D., Finegold, M. J., and Butel, J. S. (1996) Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. Mol. Carcinogen. 15, 261–269.

    Article  CAS  Google Scholar 

  13. Terradillos, O., Billet, O., Renard, C. A., Levy, R., Molina, T., Briand, P., et al. (1997) The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene. 14, 395–404.

    Article  CAS  PubMed  Google Scholar 

  14. Koike, K., Moriya, K., Yotsuyanagi, H., Iino, S., and Kurokawa, K. (1994) Induction of cell cycle progression by hepatitis B virus HBx gene expression in quiescent mouse fibroblasts. J. Clin. Invest. 94, 44–49.

    Article  CAS  PubMed  Google Scholar 

  15. Benn, J. and Schneider, R. J. (1995) Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. Proc. Natl. Acad. Sci USA 92, 11215–11219.

    Article  CAS  PubMed  Google Scholar 

  16. Fischer, M., Runkel, L., and Schaller, H. (1995) HBx protein of hepatitis B virus interacts with the C-terminal portion of a novel human proteasome alpha-subunit. Virus. Genes, 10, 99–102.

    Article  CAS  PubMed  Google Scholar 

  17. Huang, J., Kwong, J., Sun, E. C., and Liang, T. J. (1996) Proteasome complex as a potential cellular target of hepatitis B virus X protein. J. Virol. 70, 5582–5591.

    CAS  PubMed  Google Scholar 

  18. Sirma, H., Weil, R., Rosmorduc, O., Urban, S., Israel, A., Kremsdorf, D., et al. (1998) Cytosol is the prime compartment of hepatitis B virus X protein where it colocalizes with the proteasome. Oncogene. 16, 2051–2063.

    Article  CAS  PubMed  Google Scholar 

  19. Lee, T. H., Elledge, S. J., and Butel, J. S. (1995) Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. J. Virol. 69, 1107–1114.

    CAS  PubMed  Google Scholar 

  20. Qadri, I., Conaway, J. W., Conaway, R. C., Schaack, J., and Siddiqui, A. (1996) Hepatitis B virus transactivator protein, HBx, associates with the components of TFIIH and stimulates the DNA helicase activity of TFIIH. Proc. Natl. Acad. Sci. USA 93, 10,578–10,583.

    Article  CAS  PubMed  Google Scholar 

  21. Feitelson, M. A., Zhu, M., Duan, L. X., and London, W. T. (1993) Hepatitis B x antigen and p53 are associated in vitro and in liver tissues from patients with primary hepatocellular carcinoma. Oncogene. 8, 1109–1117.

    CAS  PubMed  Google Scholar 

  22. Wang, X. W., Forrester, K., Yeh, H., Feitelson, M. A., Gu, J. R., and Harris, C. C. (1994) Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc. Natl. Acad. Sci USA 91, 2230–2234.

    Article  CAS  PubMed  Google Scholar 

  23. Takada, S., Tsuchida, N., Kobayashi, M., and Koike, K. (1995) Disruption of the function of tumor-suppressor gene p53 by the hepatitis B virus X protein and hepatocarcinogenesis. J. Cancer Res. Clin. Oncol. 121, 593–601.

    Article  CAS  PubMed  Google Scholar 

  24. Truant, R., Antunovic, J., Greenblatt, J., Prives, C., and Cromlish, J. A. (1995) Direct inhibition of the hepatitis B virus HBx protein with p53 leads to inhibition by HBx of p53 response element-directed transactivation. J. Virol. 69, 1851–1859.

    CAS  PubMed  Google Scholar 

  25. Siddiqui, A., Jameel, S., and Mapoles, J. (1987) Expression of the hepatitis B virus X gene in mammalian cells. Proc. Natl. Acad. Sci USA 84, 2513–2517.

    Article  CAS  PubMed  Google Scholar 

  26. Twu, J. S. and Schloemer, R. H. (1987) Transcriptional trans-activating function of hepatitis B virus. J. Virol. 61, 3448–3453.

    CAS  PubMed  Google Scholar 

  27. Spandau, D. F. and Lee, C. H. (1988) trans-activation of viral enhancers by the hepatitis B virus X protein. J. Virol. 62, 427–434.

    CAS  PubMed  Google Scholar 

  28. Seto, E., Yen, T. S., Peterlin, B. M., and Ou, J. H. (1988) Trans-activation of the human immunodeficiency virus long terminal repeat by the hepatitis B virus X protein. Proc. Natl. Acad. Sci USA 85, 8286–8290.

    Article  CAS  PubMed  Google Scholar 

  29. Twu, J. S., Chu, K., and Robinson, W. S. (1989) Hepatitis B virus X gene activates kappa B-like enhancer sequences in the long terminal repeat of human immunodeficiency virus 1. Proc. Natl. Acad. Sci. USA, 86, 5168–5172.

    Article  CAS  PubMed  Google Scholar 

  30. Colgrove, R., Simon, G., and Ganem, D. (1989) Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. J. Virol. 63, 4019–4026.

    CAS  PubMed  Google Scholar 

  31. Twu, J. S. and Robinson, W. S. (1989) Hepatitis B virus X gene can transactivate heterologous viral sequences. Proc. Natl. Acad. Sci. USA, 86, 2046–2050.

    Article  CAS  PubMed  Google Scholar 

  32. Levrero, M., Balsano, C., Natoli, G., Avantaggiati, M. L., and Elfassi, E. (1990) Hepatitis B virus X protein transactivates the long terminal repeats of human immunodeficiency virus types 1 and 2. J. Virol. 64, 3082–3086.

    CAS  PubMed  Google Scholar 

  33. Lucito, R. and Schneider, R. J. (1992) Hepatitis B virus X protein activates transcription factor NF-kappa B without a requirement for protein kinase C. J. Virol. 66, 983–991.

    CAS  PubMed  Google Scholar 

  34. Aufiero, B. and Schneider, R. J. (1990) The hepatitis B virus X-gene product trans-activates both RNA polymerase II and III promoters. EMBO J. 9, 497–504.

    CAS  PubMed  Google Scholar 

  35. Cross, J. C., Wen, P., and Rutter, W. J. (1993) Transactivation by hepatitis B virus X protein is promiscuous and dependent on mitogen-activated cellular serine/ threonine kinases. Proc. Natl. Acad. Sci USA 90, 8078–8082.

    Article  CAS  PubMed  Google Scholar 

  36. Twu, J. S., Lai, M. Y., Chen, D. S., and Robinson, W. S. (1993) Activation of protooncogene c-jun by the X protein of hepatitis B virus. Virology. 192, 346–350.

    Article  CAS  PubMed  Google Scholar 

  37. Luber, B., Lauer, U., Weiss, L., Hohne, M., Hofschneider, P. H., and Kekule, A. S. (1993) The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C. Res. Virol. 144, 311–321.

    Article  CAS  PubMed  Google Scholar 

  38. Natoli, G., Avantaggiati, M. L., Chirillo, P., Costanzo, A., Artini, M., Balsano, C., et al. (1994) Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX. Mol. Cell Biol, 14, 989–998.

    CAS  PubMed  Google Scholar 

  39. Doria, M., Klein, N., Lucito, R., and Schneider, R. J. (1995) The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of transcription factors. EMBO J. 14, 4747–4757.

    CAS  PubMed  Google Scholar 

  40. Williams, J. S. and Andrisani, O. M. (1995) The hepatitis B virus X protein targets the basic region-leucine zipper domain of CREB. Proc. Natl. Acad. Sci USA 92, 3819–3823.

    Article  CAS  PubMed  Google Scholar 

  41. Cheong, J. H., Yi, M., Lin, Y., and Murakami, S. (1995) Human RPB5, a subunit shared by eukaryotic nuclear RNA polymerases, binds human hepatitis B virus X protein and may play a role in X transactivation. EMBO J. 14, 143–150.

    CAS  PubMed  Google Scholar 

  42. Qadri, I., Maguire, H. F., and Siddiqui, A. (1995) Hepatitis B virus transactivator protein X interacts with the TATA-binding protein. Proc. Natl. Acad. Sci USA 92, 1003–1007.

    Article  CAS  PubMed  Google Scholar 

  43. Kekulë, A. S., Lauer, U., Weiss, L., Luber, B., and Hofschneider, P. H. (1993) Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway. Nature. 361, 742–745.

    Article  PubMed  Google Scholar 

  44. Benn, J. and Schneider, R. J. (1994) Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade. Proc. Natl. Acad. Sci. USA, 91, 10,350–10,354.

    Article  CAS  PubMed  Google Scholar 

  45. Wang, H. D., Trivedi, A., and Johnson, D. L. (1997) Hepatitis B virus X protein induces RNA polymerase III-dependent gene transcription and increases cellular TATA-binding protein by activating the Ras signaling pathway. Mol. Cell. Biol. 17, 6838–6846.

    CAS  PubMed  Google Scholar 

  46. Chirillo, P., Pagano, S., Natoli, G., Puri, P. L., Burgio, V. L., Balsano, C., et al. (1997) The hepatitis B virus X gene induces p53-mediated programmed cell death. Proc. Natl. Acad. Sci USA 94, 8162–8167.

    Article  CAS  PubMed  Google Scholar 

  47. Kim, H., Lee, H., and Yun, Y. (1998) X-gene product of hepatitis B virus induces apoptosis in liver cells. J. Biol. Chem, 273, 381–385.

    Article  CAS  PubMed  Google Scholar 

  48. Su, F. and Schneider, R. J. (1997) Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha. Proc. Natl. Acad. Sci USA 94, 8744–8749.

    Article  CAS  PubMed  Google Scholar 

  49. Lane, D. P. (1992) Cancer. p53, guardian of the genome. Nature. 358, 15–16.

    Article  CAS  PubMed  Google Scholar 

  50. Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., et al. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in Ataxia-Telangiectasia. Cell. 71, 587–597.

    Article  CAS  PubMed  Google Scholar 

  51. Lee, S., Elenbase, B., Levine, A., and Griffith, J. (1995) p53 and Its 14kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell. 81, 1013–1020.

    Article  CAS  PubMed  Google Scholar 

  52. Wang, X. W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J. M., et al.(1995) p53 Modulation of TFIIH-associated nucleotide excision repair activity. Nature Genet. 10, 188–195.

    Article  CAS  PubMed  Google Scholar 

  53. Livingstone, L. R., White, A., Sprouse, J., Livanos, E., Jacks, T., and Tlsty, T. D. (1992) Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 70, 923–935.

    Article  CAS  PubMed  Google Scholar 

  54. Yin, Y., Tainsky, M. A., Bischoff, F. Z., Strong, L. C., and Wahl, G. M. (1992) Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 70, 937–948.

    Article  CAS  PubMed  Google Scholar 

  55. Yonish-Rouach, E., Resnitzky, D., Lotem, J., Sachs, L., Kimchi, A., and Oren, M. (1991) Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 352, 345–347.

    Article  CAS  PubMed  Google Scholar 

  56. Shaw, P., Bovey, R., Tardy, S., Sahli, R., Sordat, B., and Costa, J. (1992) Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc. Natl. Acad. Sci USA 89, 4495–4499.

    Article  CAS  PubMed  Google Scholar 

  57. Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 26, 239–257.

    Article  CAS  PubMed  Google Scholar 

  58. Clarke, A. R., Purdie, C. A., Harrison, D. J., Morris, R. G., Bird, C. C., Hooper, M. L., et al. (1993) Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature. 362, 849–852.

    Article  CAS  PubMed  Google Scholar 

  59. Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., and Jacks, T. (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 362, 847–849.

    Article  CAS  PubMed  Google Scholar 

  60. Symonds, H., Krall, L., Remington, L., Saenz-Robles, M., Lowe, S., Jacks, T., et al. (1994) p53-Dependent apoptosis suppresses tumor growth and progression in vivo. Cell. 78, 703–711.

    Article  CAS  PubMed  Google Scholar 

  61. Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., et al. (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 379, 88–91.

    Article  CAS  PubMed  Google Scholar 

  62. Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, C. C. (1991) p53 Mutations in human cancers. Science. 253, 49–53.

    Article  CAS  PubMed  Google Scholar 

  63. Levine, A. J., Momand, J., and Finlay, C. A. (1991) The p53 tumour suppressor gene. Nature. 351, 453–456.

    Article  CAS  PubMed  Google Scholar 

  64. Greenblatt, M. S., Bennett, W. P., Hollstein, M., and Harris, C. C. (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54, 4855–4878.

    CAS  PubMed  Google Scholar 

  65. Lee, J. M. and Bernstein, A. (1993) p53 mutations increase resistance to ionizing radiation. Proc. Natl. Acad. Sci. USA 90, 5742–5746.

    Article  CAS  PubMed  Google Scholar 

  66. Lowe, S. W., Ruley, H. E., Jacks, T., and Housman, D. E. (1993) p53-Dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 74, 957–967.

    Article  CAS  PubMed  Google Scholar 

  67. Lowe, S. W., Bodis, S., McClatchey, A., Remington, L., Ruley, H. E., Fisher, D. E., et al. (1994) p53 Status and the efficacy of cancer therapy in vivo. Science. 266, 807–810.

    Article  CAS  PubMed  Google Scholar 

  68. Wang, X. W. and Harris, C. C. (1996) TP53 tumour suppressor gene: clues to molecular carcinogenesis and cancer therapy. Cancer Surveys. 28, 169–196.

    CAS  PubMed  Google Scholar 

  69. Ueda, H., Ullrich, S. J., Gangemi, J. D., Kappel, C. A., Ngo, L., Feitelson, M. A., et al. (1995) Functional inactivation but not structural mutation of p53 causes liver cancer. Nature Genet. 9, 41–47.

    Article  CAS  PubMed  Google Scholar 

  70. Elmore, L. W., Hancock, A. R., Chang, S. F., Wang, X. W., Chang, S., Callahan, C. P., et al. (1997) Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proc. Natl. Acad. Sci. USA, 94, 14,707–14,712.

    Article  CAS  PubMed  Google Scholar 

  71. Lin, Y., Nomura, T., Yamashita, T., Dorjsuren, D., Tang, H., and Murakami, S. (1997) The transactivation and p53-interacting functions of hepatitis B virus X protein are mutually interfering but distinct. Cancer Res. 57, 5137–5142.

    CAS  PubMed  Google Scholar 

  72. Wang, X. W., Vermeulen, W., Coursen, J. D., Gibson, M., Lupold, S. E., Forrester, K., et al. (1996) The XPB and XPD helicases are components of the p53-mediated apoptosis pathway. Genes Dev. 10, 1219–1232.

    Article  CAS  PubMed  Google Scholar 

  73. Wang, X. W., Gibson, M. K., Vermeulen, W., Yeh, H., Forrester, K., Sturzbecher, H. W., et al. (1995) Abrogation of p53-induced apoptosis by the hepatitis B virus X gene. Cancer Res. 55, 6012–6016.

    CAS  PubMed  Google Scholar 

  74. Takada, S., Kaneniwa, N., Tsuchida, N., and Koike, K. (1996) Hepatitis B virus X gene expression is activated by X protein but repressed by p53 tumor suppressor gene product in the transient expression system. Virology. 216, 80–89.

    Article  CAS  PubMed  Google Scholar 

  75. Takada, S., Kaneniwa, N., Tsuchida, N., and Koike, K. (1997) Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells. Oncogene. 15, 1895–1901.

    Article  CAS  PubMed  Google Scholar 

  76. Hosono, S., Chou, M. J., Lee, C. S., and Shih, C. (1993) Infrequent mutation of p53 gene in hepatitis B virus positive primary hepatocellular carcinomas. Oncogene. 8, 491–496.

    CAS  PubMed  Google Scholar 

  77. Henkler, F., Waseem, N., Golding, M. H., Alison, M. R., and Koshy, R. (1995) Mutant p53 but not Hepatitis B virus X protein is present in Hepatitis B virus-related human hepatocellular carcinoma. Cancer Res. 55, 6084–6091.

    CAS  PubMed  Google Scholar 

  78. Greenblatt, M. S., Feitelson, M. A., Zhu, M., Bennett, W. P., Welsh, J. A., Jones, R., et al. (1997) Integrity of p53 in hepatitis B x antigen-positive and-negative hepatocellular carcinomas. Cancer Res. 57, 426–432.

    CAS  PubMed  Google Scholar 

  79. Huang, L. C., Clarkin, K. C., and Wahl, G. M. (1996) Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc. Natl. Acad. Sci. USA, 93, 4827–4832.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD

    Xin Wei Wang

Authors
  1. Xin Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Liver Surgery Section, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    Nagy A. Habib

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Wei Wang, X. (2000). Abrogation of p53-Induced Apoptosis by the Hepatitis B Virus X Gene. In: Habib, N.A. (eds) Hepatocellular Carcinoma. Methods in Molecular Medicine™, vol 45. Humana Press. https://doi.org/10.1385/1-59259-079-9:57

Download citation

  • DOI: https://doi.org/10.1385/1-59259-079-9:57

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-785-4

  • Online ISBN: 978-1-59259-079-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation