Properties of tumour suppressor p53 in murine hepatocyte lines transformed by hepatitis B virus X protein.
Persistent infection by hepatitis B virus (HBV) correlates with the prevalence of hepatocellular carcinoma. It has recently been demonstrated that the complete viral genome very efficiently transforms the immortalized murine hepatocyte line FMH202 in vitro. Here it is shown that the viral transactivating protein X (HBx) is sufficient to transform FMH202 cells, albeit with lower efficiency. Clonal cell lines expressing HBx mRNA in moderate or high amounts grew in soft agar and formed tumours in nude mice. Growth efficiency in soft agar of HBx transformed cell lines was much lower than that of cell lines transformed with the complete genome, and latency of tumour induction in nude mice was significantly longer after inoculation of HBx than of HBV transformed FMH202 cell lines. A marker of complete transformation, p53, was found to be phosphorylated more strongly in HBx transfected cell lines than in controls, and a cellular kinase was found to be associated with p53 complexes from HBx transformed cell lines. p53 was of wild-type conformation and was located in the nucleus of transformed cells.
Schaefer
S
S
Institute of Medical Virology, Justus-Liebig University, Giessen, Germany. stephan.schaefer@viro.med.uni-giessen.de
Seifer
M
M
Grimmsmann
T
T
Fink
L
L
Wenderhold
S
S
Höhne
M W
MW
Gerlich
W H
WH
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D008099:Liver / Q000378:metabolism / Q000821:virology*; D008114:Liver Neoplasms, Experimental / Q000209:etiology; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D011494:Protein Kinases