Feitelson Mark Alan, Reis Helena M G P V, Liu Jie, Lian Zhaorui, Pan Jingbo
Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Front Biosci. 2005 May 1;10:1558-72. doi: 10.2741/1640.
Hepatitis B and related viruses that infect mammalian hosts encode the "X" protein that has been shown to contribute importantly to the pathogenesis of chronic liver disease (CLD) and to the development of hepatocellular carcinoma (HCC). In a variety of tissue culture systems, hepatitis B virus (HBV) X antigen, or HBxAg, has been shown to trigger apoptosis, while other evidence suggests that HBxAg inhibits apoptosis and stimulates the cell cycle by constitutively activating a number of signaling pathways that are important for hepatocellular growth and survival. These apparently contrasting properties of HBxAg may be associated with differences in the X protein itself, since carboxy-terminal truncated forms of HBxAg appear to be associated with HCC lesions. Alternatively, or in addition, these differences may be due to the cell type, state of cell differentiation, and whether expression occurs in resting or dividing cells. Further, the association between HBxAg expression and chromosomal instability, may also contribute to the apparently contrasting fates of HBxAg positive cells. It is proposed that in many of these systems, the different outcomes of HBxAg expression may be due to the nature of the cellular response to HBxAg, and not due to differences in the fundamental properties of HBxAg, the latter of which promote cell survival, cell cycle progression, and the development of HCC.
感染哺乳动物宿主的乙型肝炎及相关病毒编码“X”蛋白，该蛋白已被证明对慢性肝病（CLD）的发病机制以及肝细胞癌（HCC）的发展起着重要作用。在多种组织培养系统中，乙型肝炎病毒（HBV）X抗原，即HBxAg，已被证明可引发细胞凋亡，而其他证据表明，HBxAg可抑制细胞凋亡并通过持续激活一些对肝细胞生长和存活至关重要的信号通路来刺激细胞周期。HBxAg这些明显相反的特性可能与X蛋白本身的差异有关，因为HBxAg的羧基末端截短形式似乎与HCC病变有关。或者，或者此外，这些差异可能是由于细胞类型、细胞分化状态以及表达是发生在静止细胞还是分裂细胞中。此外，HBxAg表达与染色体不稳定性之间的关联，也可能导致HBxAg阳性细胞明显不同的命运。有人提出，在许多这些系统中，HBxAg表达的不同结果可能是由于细胞对HBxAg的反应性质，而不是由于HBxAg基本特性的差异，后者促进细胞存活、细胞周期进展以及HCC的发展。
