Skip to main content
SpringerLink
Log in

HBx gene of hepatitis B virus induces liver cancer in transgenic mice

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

THE exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility by placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tiollais, P., Pourcel, C. & Oejean, A. Nature 317, 489–495 (1985).

    Article  ADS  CAS  Google Scholar 

  2. Beasley, R. B. & Hwang, L.-Y. in Viral Hepatitis and Liver Disease (eds Vyas, G. N.) 209–224 (Grune & Stratton, Florida, 1984).

    Google Scholar 

  3. Beasley, R. P., Hwang, L.-Y., Linn, C. C. & Chien, C. S. Lancet ii, 1129–1133 (1981).

    Article  Google Scholar 

  4. Dejean, A., Sonigo, P., Wain-Hobson, S. & Tiollais, P. Proc. natn. Acad. Sci. U.S.A. 81, 5350–5354 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Rogler, C. E. et al. Science 230, 319–322 (1985).

    Article  ADS  CAS  Google Scholar 

  6. Chisari, F. V. et al. J. Virol. 60, 880–887 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Chisari, F. V. et al. Cell 59, 1145–1156 (1989).

    Article  CAS  Google Scholar 

  8. de The, H., Marchio, A., Tiollais, P. & Dejean, A. Nature 330, 667–670 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Hsu, T. Y. et al. Cell 55, 627–635 (1988).

    Article  CAS  Google Scholar 

  10. Fourel, G. et al. Nature 347, 294–298 (1990).

    Article  ADS  CAS  Google Scholar 

  11. Wollersheim, M., Debelka, U. & Hofschneider, P. H. Oncogene 3, 545–552 (1988).

    CAS  PubMed  Google Scholar 

  12. Twu, J.-S. & Schloemer, R. H. J. Virol. 61, 3448–3453 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Spandau, D. F. & Lee, C. H. J. Virol. 62, 427–434 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Seto, E., Mitchell, P. J. & Yen, T. S. B. Nature 344, 72–74 (1990).

    Article  ADS  CAS  Google Scholar 

  15. Vogel, J., Hinrichs, S. H., Reynolds, R. K., Luciw, P. A. & Jay, G. Nature 335, 606–611 (1988).

    Article  ADS  CAS  Google Scholar 

  16. Nerenberg, M., Hinrichs, S. K., Reynolds, R. K., Khoury, G. & Jay, G. Science 237, 1324–1329 (1987).

    Article  ADS  CAS  Google Scholar 

  17. Green, J. E., Hinrichs, S. H., Vogel, J. & Jay, G. Nature 341, 72–74 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Koike, K., Hinrichs, S. H., Isselbacher, K. J. & Jay, G. Proc. natn. Acad. Sci. U.S.A. 86, 5615–5619 (1989).

    Article  ADS  CAS  Google Scholar 

  19. Small, J. A., Scangos, G., Cork, L., Jay, G. & Khoury, G. Cell 46, 13–18 (1986).

    Article  CAS  Google Scholar 

  20. Small, J. A., Khoury, G., Jay, G., Howley, P. & Scangos, G. A. Proc. natn. Acad. Sci. U.S.A. 83, 8288–8292 (1986).

    Article  ADS  CAS  Google Scholar 

  21. Fujiyama, A. et al. Nucleic Acids Res. 11, 4601–4610 (1983).

    Article  CAS  Google Scholar 

  22. Shaul, Y., Rutter, W. J. & Laub, O. EMBO J. 4, 427–430 (1985).

    Article  CAS  Google Scholar 

  23. Treinin, M. & Laub, O. Molec. cell. Biol. 7, 545–548 (1987).

    Article  CAS  Google Scholar 

  24. Kaneko, S. & Miller, R. H. J. Virol. 62, 3979–3984 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Dejean, A., Lugassy, C., Zafrani, S., Tiollais, P. & Brechot, C. J. gen. Virol. 65, 651–655 (1984).

    Article  Google Scholar 

  26. Koike, K., Akatsuka, T. & Miyamura, T. Virology 163, 233–235 (1988).

    Article  CAS  Google Scholar 

  27. Klimek, F., Mayer, D. & Bannasch, P. Carcinogenesis 5, 265–268 (1984).

    Article  CAS  Google Scholar 

  28. Brooks, P. N. & Roe, F. J. C. in Digestive System (eds Jones, T. C., Mohr, U. & Hunt, R. D.) 47–52 (Springer, Berlin/Heidelberg, 1985).

    Book  Google Scholar 

  29. Bannasch, P., Zerban, H. & Hacker, H. J. in Digestive System (eds Jones, T. C., Mohr, U. & Hunt, R. D.) 10–30 (Springer, Berlin/Heidelberg, 1985).

    Book  Google Scholar 

  30. Beckar, F. F. Cancer Res. 42, 3918–3923 (1982).

    Google Scholar 

  31. Popp, J. A. in Digestive System (eds Jones, T. C., Mohr, U. & Hunt, R. D.) 39–46 (Springer, Berlin/Heidelberg, 1985).

    Book  Google Scholar 

  32. Chisari, F. V. et al. Science 230, 1157–1160 (1985).

    Article  ADS  CAS  Google Scholar 

  33. Babinet, C., Farza, H., Morello, D., Hadchonel, M. & Pourcel, C. Science 230, 1160–1163 (1985).

    Article  ADS  CAS  Google Scholar 

  34. Burk, R. D., DeLoiz, J. A., Elawady, M. K. & Gerhart, J. D. J. Virol. 62, 649–654 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Farza, H. et al. J. Virol. 62, 4149–4152 (1988).

    Google Scholar 

  36. Araki, K. et al. Proc. natn. Acad Sci. U.S.A. 86, 207–211 (1989).

    Article  ADS  CAS  Google Scholar 

  37. Lee, T.-H. et al. J. Virol. 64, 5939–5947 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Cosman, D., Kress, M., Khoury, G. & Jay, G. Proc. natn. Acad. Sci. U.S.A. 79, 4947–4951 (1982).

    Article  ADS  CAS  Google Scholar 

  39. Kress, M., Cosman, D., Khoury, G. & Jay, G. Cell 34, 189–196 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Kazuhiko Koike & Izumu Saito

    Present address: First Department of Internal Medicine, University of Tokyo, Tokyo, 113, Japan

  2. Gilbert Jay: To whom correspondence should be addressed.

Authors and Affiliations

  1. Laboratory of Virology, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland, 20855, USA

    Chang-Min Kim, Kazuhiko Koike & Gilbert Jay

  2. Laboratory of Hepatitis Viruses, Department of Enteroviruses, National Institute of Health, Tokyo, 141, Japan

    Tatsuo Miyamura

Authors
  1. Chang-Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuhiko Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Izumu Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatsuo Miyamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gilbert Jay
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, CM., Koike, K., Saito, I. et al. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351, 317–320 (1991). https://doi.org/10.1038/351317a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/351317a0

  • Springer Nature Limited

This article is cited by

Search

Navigation