1887

Abstract

Despite the extensive studies on the roles of hepatitis B virus (HBV) X protein (HBx) in the development of hepatocellular carcinomas (HCCs), the mechanisms by which HBx contributes to HCC remain controversial. In this study, the effect of HBx on the G–S checkpoint control depending on the status of p53 was compared. Transcription of p21 was activated by HBx in the presence of functional p53 in a dose-dependent manner. However, it was repressed by HBx when p53 was absent or present at a low level. Furthermore, the growth rate of the HBx-expressing NIH3T3 cell lines compared with that of the parental cells was decreased when p53 was upregulated by a DNA-damaging agent, cisplatin, whereas it increased approximately twofold when p53 was present at a very low level. Thus, the opposite effects of HBx on the regulation of the cell cycle depending on the status of p53 might be important to understand the progression of hepatic diseases in HBV-positive patients.

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2002-11-01
2019-10-20
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References

  1. Ahn, J. Y., Chung, E. Y., Kwun, H. J. & Jang, K. L. ( 2001; ). Transcriptional repression of p21waf1 promoter by hepatitis B virus X protein via a p53-independent pathway. Gene 275, 163-168.[CrossRef]
    [Google Scholar]
  2. Benn, J. & Schneider, R. J. ( 1994; ). Hepatitis B virus HBx protein activates Ras–GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade. Proceedings of the National Academy of Sciences, USA 91, 10350-10354.[CrossRef]
    [Google Scholar]
  3. Chang, J., Yang, S. H., Cho, Y. G., Hwang, S. B., Hahn, Y. S. & Sung, Y. C. ( 1998; ). Hepatitis C virus core from two different genotypes has an oncogenic potential but not sufficient for transforming primary rat embryo fibroblasts in cooperation with the H-ras oncogene. Journal of Virology 72, 3060-3065.
    [Google Scholar]
  4. Chomczynski, P. & Sacchi, N. ( 1987; ). Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Analytical Biochemistry 162, 156-159.
    [Google Scholar]
  5. Datto, M. B., Yu, Y. & Wang, X. F. ( 1995; ). Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cip1/p21 promoter. Journal of Biological Chemistry 270, 28623-28628.[CrossRef]
    [Google Scholar]
  6. Eapen, A. K., Henry, M. K., Quelle, D. E. & Quelle, F. W. ( 2001; ). DNA damage-induced G1 arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2. Molecular and Cellular Biology 21, 6113-6121.[CrossRef]
    [Google Scholar]
  7. El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W. & Vogelstein, B. ( 1993; ). WAF1, a potential mediator of p53 tumor suppression. Cell 4, 817-825.
    [Google Scholar]
  8. El-Deiry, W. S., Harper, J. W., O′Connor, P. M., Velculescu, V. E., Canman, C. E., Jackman, J., Pietenpol, J. A., Burrell, M., Hill, D. E., Wang, Y., Wiman, K. G., Mercer, W. E., Kastan, M. B., Kohn, K. W., Elledge, S. J., Kinzler, K. W. & Vogelstein, B. ( 1994; ). WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Research 54, 1169-1174.
    [Google Scholar]
  9. Galbiati, F., Volonte, D., Liu, J., Capozza, F., Frank, P. G., Zhu, L., Pestell, R. G. & Lisanti, M. P. ( 2001; ). Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism. Molecular Biology of the Cell 12, 2229-2244.[CrossRef]
    [Google Scholar]
  10. Ganem, D. & Varmus, H. E. ( 1987; ). The molecular biology of the hepatitis B viruses. Annual Review of Biochemistry 56, 651-693.[CrossRef]
    [Google Scholar]
  11. Han, J., Yoo, H. Y., Choi, B. H. & Rho, H. M. ( 2000; ). Selective transcriptional regulations in the human liver cell by hepatitis B viral X protein. Biochemical and Biophysical Research Communications 272, 525-530.[CrossRef]
    [Google Scholar]
  12. Jackson, A. L. & Loeb, L. A. ( 1998; ). On the origin of multiple mutations in human cancers. Seminars in Cancer Biology 8, 421-429.[CrossRef]
    [Google Scholar]
  13. Jia, L., Wang, X. W. & Harris, C. C. ( 1999; ). Hepatitis B virus X protein inhibits nucleotide excision repair. International Journal of Cancer 80, 875-879.[CrossRef]
    [Google Scholar]
  14. Kaufmann, W. K., Behe, C. I., Golubovskaya, V. M., Byrd, L. L., Albright, C. D., Borchet, K. M., Presnell, S. C., Coleman, W. B., Grisham, J. W. & Smith, G. J. ( 2001; ). Aberrant cell cycle checkpoint function in transformed hepatocytes and WB-F344 hepatic epithelial stem-like cells. Carcinogenesis 8, 1257-1269.
    [Google Scholar]
  15. Kim, C. M., Koike, K., Saito, I., Miyamura, T. & Gilbert, J. ( 1991; ). HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351, 317-320.[CrossRef]
    [Google Scholar]
  16. Lee, S. G. & Rho, H. M. ( 2000; ). Transcriptional repression of the human p53 gene by hepatitis B viral X protein. Oncogene 19, 468-471.[CrossRef]
    [Google Scholar]
  17. Lee, C. W., Sørensen, T. S., Shikama, N. & La Thangue, N. B. ( 1998; ). Functional interplay between p53 and E2F through co-activator p300. Oncogene 16, 2695-2710.[CrossRef]
    [Google Scholar]
  18. McDonald, E. R.III & El-Deiry, W. S. ( 2001; ). Checkpoint genes in cancer. Annals of Medicine 33, 113-122.[CrossRef]
    [Google Scholar]
  19. Martin-Caballero, J., Flores, J. M., Garcia-Palencia, P. & Serrano, M. ( 2001; ). Tumor susceptibility of p21Waf1 /Cip1-deficient mice. Cancer Research 61, 6234-6238.
    [Google Scholar]
  20. Morgan, S. E., Kim, R., Wang, P. C., Bhat, U. G., Kusumoto, H., Lu, T. & Beck, W. T. ( 2000; ). Differences in mutant p53 protein stability and functional activity in teniposide-sensitive and -resistant human leukemic CEM cells. Oncogene 19, 5010-5019.[CrossRef]
    [Google Scholar]
  21. Papakyriakou, P., Tzardi, M., Valatas, V., Kanavaros, P., Karydi, E., Notas, G., Xidakis, C. & Kouroumalis, E. ( 2002; ). Apoptosis and apoptosis related proteins in chronic viral liver disease. Apoptosis 7, 133-141.[CrossRef]
    [Google Scholar]
  22. Park, U. S., Park, S. K., Lee, Y. I., Park, J. G. & Lee, Y. I. ( 2000; ). Hepatitis B virus-X protein upregulates the expression of p21waf1/cip1 and prolongs G1→S transition via a p53-independent pathway in human hepatoma cells. Oncogene 19, 3384-3394.[CrossRef]
    [Google Scholar]
  23. Pinski, J., Parikh, A., Bova, G. S. & Isaacs, J. T. ( 2001; ). Therapeutic implications of enhanced G0/G1 checkpoint control induced by coculture of prostate cancer cells with osteoblasts. Cancer Research 61, 6372-6376.
    [Google Scholar]
  24. Prost, S., Ford, J. M., Taylor, C., Doig, J. & Harrison, D. J. ( 1998; ). Hepatitis B x protein inhibits p53-dependent DNA repair in primary mouse hepatocytes. Journal of Biological Chemistry 273, 33327-33332.[CrossRef]
    [Google Scholar]
  25. Pruitt, K. & Der, C. J. ( 2001; ). Ras and Rho regulation of the cell cycle and oncogenesis. Cancer Letters 171, 1-10.[CrossRef]
    [Google Scholar]
  26. Sohn, S., Jaitovitch-Groisman, I., Benlimame, N., Galipeau, J., Batist, G. & Alaoui-Jamli, M. A. ( 2000; ). Retroviral expression of the hepatitis B virus x gene promotes liver cell susceptibility to carcinogen-induced site specific mutagenesis. Mutation Research 460, 17-28.[CrossRef]
    [Google Scholar]
  27. Su, F. & Schneider, R. J. ( 1996; ). Hepatitis B virus HBx protein activates transcription factor NF-κB by acting on multiple cytoplasmic inhibitors of related proteins. Journal of Virology 70, 4558-4566.
    [Google Scholar]
  28. Wang, X. W., Forrester, K., Yeh, H., Feitelson, M. A., Gu, J. R. & Harris, C. C. ( 1994; ). Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proceedings of the National Academy of Sciences, USA 91, 2230-2234.[CrossRef]
    [Google Scholar]
  29. Yen, A., Sturgill, R., Varvayanis, S. & Chern, R. ( 1996; ). FMS(CSF-1 receptor) prolongs cell cycle and promotes retinoic acid-induced hypophosphorylation of retinoblastoma protein, G1 arrest, and cell differentiation. Experimental Cell Research 229, 111-125.[CrossRef]
    [Google Scholar]
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