Altered signal transduction in human hepatocellular carcinoma

摘要

Primary hepatocellular carcinoma (HCC) is principally caused by chronic infection with hepatitis B (HBV), and hepatitis C (HCV) viruses (Fig. 1). Persistent infection with these two agents produces inflammation, cell turnover, regeneration and growth, fibrosis and, eventually, cirrhosis. In these settings, additional genetic mutations may occur which then lead to the development of HCC. However, other causes of HCC include cirrhosis due to ethanol abuse, metabolic and hormonal agents such as haemochromatosis, and anabolic steroid use, as well as environmental factors such as aflatoxin exposure. All act at various levels of this transformation process as shown in Fig. 1. For example, HBV participates in the hepatocyte transformation by (1) producing chronic inflammation and cell turnover, (2) expression of the HBx protein which is a viral specific transcriptional transactivator, and may upregulate cellular genes associated with cell growth and, (3) HBV integrates into the hepatocyte DNA and this event leads togenomic instability due to deletions, point mutation, duplication, and translocation of both viral and cellular genes during the integration process.