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Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts

Oncogene volume 19, pages 1173–1180 (2000)Cite this article

Abstract

Epidemiology shows a clear correlation between chronic infection with the hepatitis B virus (HBV) and development of hepatocellular carcinoma (HCC). The potential role of the transactivating hepatitis B virus X protein (HBx) in transformation by HBV is controversial. Here we report that HBx suppresses transformation of primary rat embryo fibroblasts (REFs). Cooperating oncogenes like c-Ha-ras and c-myc transform REF very efficiently but cotransfection with HBx suppressed transformation of REFs down to 5%. Similarly, transfection of HBx together with the cooperating oncogenes Ha-ras and SV40 LTAg or c-Ha-ras and mutant p53 reduced the number of foci to 13%. Comparable results were obtained with HBx in the context of the whole HBV. Suppression of focus formation in REF could be partly relieved by cotransfection of apoptosis inhibitors Bcl-2 or E1B. However, cotransfection of apoptosis inhibitors crmA and p35 did not influence the proapoptotic functions of HBx. Thus, HBx may specifically activate the Bcl-2 sensitive pathway leading to apoptosis. Experiments with 13 HBx linker scanning mutants revealed that the domains necessary for HBx dependent transactivation overlap with the domains needed for the apoptotic/growth arrest functions of HBx.

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Acknowledgements

This work was supported in parts by grant 01 KI 9552 of the Bundesministerium für Forschung und Technologie and grant 01 KI 98589 of the Bundesministerium für Bildung und Forschung to S Schaefer and WH Gerlich. This work was performed in partial fulfilment of the requirements for the Ph.D. thesis of R Schuster.

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  1. Institut für Medizinische Virologie, Justus-Liebig-Universität, Frankfurter Str. 107, Gießen, D-35392, Germany

    Ralph Schuster, Wolfram H Gerlich & Stephan Schaefer

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  1. Ralph Schuster
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  2. Wolfram H Gerlich
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  3. Stephan Schaefer
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Schuster, R., Gerlich, W. & Schaefer, S. Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts. Oncogene 19, 1173–1180 (2000). https://doi.org/10.1038/sj.onc.1203417

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