MNi, BE (Feulgen staining) and immunohistochemical expression of p53 and Mib1 were assessed in 95 liver lesions representing the whole spectrum of liver carcinogenesis.
The resultant molecular changes in the ras and Wnt signal-transduction pathways, and the p53 and Rb tumor suppressor pathways significantly contribute to liver carcinogenesis
Our study was designed to assess the importance of p53 aberrations in HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant role.
In Japan, p53 gene alterations seem to be a late event in the progression of hepatocarcinogenesis, which is often associated with persistent infection by the hepatitis C or B virus, but not usually with exposure to aflatoxin.
This study investigated the efficacy of Toxoplasma GRA16, which binds to herpes virus-associated ubiquitin-specific protease (HAUSP), in anticancer treatment, and whether the expression of GRA16 in genetically modified hepatocellular carcinoma (HCC) cells (GRA16-p53-wild HepG2 and GRA16-p53-null Hep3B) regulates PTEN because alterations in phosphatase and tensin homologue (PTEN) and p53 are vital in liver carcinogenesis and the abnormal p53 gene appears in HCC.
Moreover, p53 mutation seems to be related to the reactivation of alphafetoprotein gene to a more aggressive phenotype and to a later stage of liver carcinogenesis.
We also identified that the increase in expression of the p53 gene is related to the proliferation of hepatocytes, whereas overexpression of the c-myc and N-ras genes is associated with hepatocarcinogenesis.
Although M6p/Igf2r, Apc, and p53 have been shown to be mutated in a variety of human hepatic proliferative diseases, our results indicate that aberrations in these genes may not be necessary for liver carcinogenesis in the rat.
Therefore, ε-dA lesions may gradually accumulate in chronic liver diseases, and partially contribute to mutant p53 overexpression and excessive cell proliferation, making it a potential mechanism in oxidative stress-mediated hepatocarcinogenesis.
It is concluded that both of the non-structural genes, NS3 and NS5A, of HCV play important roles in the hepatocarcinogenesis of HCV by interacting directly or indirectly in different manners with the p53 gene.
Despite good evidence for p53 dysfunction in human hepatocellular carcinomas, little is known of the significance of p53 to normal hepatocytes and whether p53 dysfunction is relevant to early hepatocarcinogenesis.
Taken together, our data suggest that down-regulation of c-met and TGF-beta-RII may, together with p53 mutations, play a significant role in human liver carcinogenesis.
In conclusion, this study has demonstrated that nuclear accumulation of beta-catenin is a frequent progression event in human hepatocarcinogenesis which correlates with nuclear p53 accumulation and loss of membranous E-cadherin, but not with the expression pattern of established WNT-1 target genes.
By analysis of codon 249 of the p53 gene, six of 36 human hepatoma samples were found to show a G-->T transversion, suggesting that AFB(1) may be a risk factor for hepatocarcinogenesis.
The overexpression of p53 and C-myc genes might play a role in the carcinogenesis of HCC; And LHN seems a preneoplastic lesion related to hepatocarcinogenesis; No evidence supports that LC contribute directly to the hepatocarcinogenesis.
Activation of v-Myb avian myeloblastosis viral oncogene homolog-like2 (MYBL2)-LIN9 complex contributes to human hepatocarcinogenesis and identifies a subset of hepatocellular carcinoma with mutant p53.
In addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor gene is produced, abrogating the function of the tumor suppressor gene, and contributing to hepatocarcinogenesis.