Schaefer S, Seifer M, Grimmsmann T, Fink L, Wenderhold S, Höhne M W, Gerlich W H
Institute of Medical Virology, Justus-Liebig University, Giessen, Germany.
J Gen Virol. 1998 Apr;79 ( Pt 4):767-77. doi: 10.1099/0022-1317-79-4-767.
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.
乙型肝炎病毒（HBV）的持续感染与肝细胞癌的发病率相关。最近有研究表明，完整的病毒基因组在体外能非常有效地转化永生化小鼠肝细胞系FMH202。本文表明，病毒反式激活蛋白X（HBx）足以转化FMH202细胞，尽管效率较低。中等或高表达HBx mRNA的克隆细胞系能在软琼脂中生长，并在裸鼠体内形成肿瘤。HBx转化细胞系在软琼脂中的生长效率远低于用完整基因组转化的细胞系，接种HBx后裸鼠肿瘤诱导的潜伏期明显长于接种HBV转化的FMH202细胞系后的潜伏期。完全转化的标志物p53在HBx转染的细胞系中比在对照中磷酸化更强，并且发现一种细胞激酶与HBx转化细胞系的p53复合物相关。p53呈野生型构象，位于转化细胞的细胞核中。
