Hepatocellular Carcinoma

Liver cancer causes more than 500,000 deaths a year worldwide, and about 90% of primary malignant tumors of the liver are hepatocellular carcinoma. HCC is more common in men than women, by 4 - 1, and is in the top 10 in frequency of cancers in humans. Areas where there are high incidence of HBV chronic infection. 50-80% of HCC patients are chronically infected with HBV.

While the mechanism by which chronic infection is not well understood, it is thought that long term infection, characterized by continuous destruction of liver cells, followed by regrowth, eventually results in the appearance and selection for cancer cells. 90% of patients with HCC have cirrhosis of liver. Hepatocellular carcinoma may also be the result of alcohol induced cirrhosis or Hepatitis C. HCC often appears 30 - 40 years of chronic infection by HBV. Thus, there is an association between HCC and continuing liver damage and regeneration over long periods.

Research has indicated that the Hepatitis B X protein may play a large role in the development of HCC. It has been reported that the mutation and disruption of PTEN, a known tumor suppressor may be involved in tumor progression. HBx had no effect on the expression of p53,a known transcriptional activator of PTEN. However, researchers have confirmedthat the binding of the p53 protein to the PTEN promoter is decreased in HBx- transfected liver cells^.Thus, it is currently believed that HBx inliver cells down-regulates the expression of PTEN by affecting the binding of p53 to PTEN, and thus makes the infected cell more likely to become cancerous.

In other studies, X protein has also been noted to perform a variety of biological functions, such as gene transactivation, interaction with p53, interference with host DNA repair, repression of physiological proteolysis, modulation of cell proliferation and apoptosis, induction of malignant cell migration. Recently, X protein was found to increase cell's level of NF-kB. NF-kB activation induced by HBx could not only facilitate infected cell survival and HBV escape from immune clearance, but also promote liver cell malignant transformation and tumor cell advantageous growth

Source:

Hepatitis B Virus X Protein Modulates the Expression of PTEN by Inhibiting the Function of p53, a Transcriptional Activator in Liver Cells http://cancerres.aacrjournals.org/cgi/content/full/63/13/3453

Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma

http://www.wjgnet.com/1007-9327/10/356.asp