Our results suggested that ALX4 was inactivated by DNA methylation and played a tumor suppressor function through the P53 pathway in MC-LR induced liver cancer.
These results indicate that p53 is overexpressed in a majority of childhood liver cancers, but this abnormal p53 expression does not seem to be caused by mutations in the p53 gene.
Majority of AFB1 associated hepatocellular cancer cases carry TP53 mutant DNA, which is an indicator of AFB1 exposure, as well as hepatocellular cancer risk.
However, wild-type mice in which AFB1 alone was used to induce liver cancers have failed to recapitulate p53 mutations, raising the possibility that mouse DNA context may not be appropriate for the generation of AFB1-induced p53 mutations.
Our results indicate that, in liver cancer, the cytotoxic somatostatin analogue AN-238 is a powerful agent that can induce apoptosis, through sst(s) and independently of p53.
Furthermore, based on phylogenetic analysis, the characteristic mutations were found in the initiating malignant clones in the AA-implicated mouse and human liver cancers where the mutations of tumor protein p53 and Janus kinase 1 were prone to be significantly enriched in the AA-affected human tumors.
We developed liver cancer cell lines that endogenously expressed a mutant form of TP53 (R249S) or overexpressed mutant forms of STAT3 (D170Y, K348E, and Y640F) or JAK1 (S703I and L910P) and tested the abilities of pharmacologic agents to reduce activity.
A mouse model of liver cancer reveals that downregulation of mevalonate pathway gene expression by p53 occurs in premalignant hepatocytes, when p53 is needed to actively suppress tumorigenesis.
As Senegal is a country where liver cancer incidence is one of the highest in the world and where people are highly exposed to aflatoxin, we screened 15 liver cancer samples from this country for mutation at codon 249 of the p53 gene.
This study has identified some important novel ways in which WtHBx and MutHBx differentially interact with p53 and this could begin to form the cellular explanation for the association between this particular mutant and liver cancer.
We conclude that repression of GMPS by p53 through p21 is a functionally relevant part of the p53-mediated senescence program limiting tumor cell growth in liver cancer.
In a second approach, functional wild type p53 is delivered into p53-null liver cancer (Hep3B) cells, sensitizing the cells toward the p53 pathway drug, Nutlin.
One such example is hepatitis virus-induced liver cancer whereby p53 is inactivated upon the binding of a specific viral protein, leading to the loss of its tumor suppressive activity.
A joint effect between the MDM2 and TP53 polymorphisms and an increased risk of liver cancer was detected, with the odds ratio for the presence of both MDM2 309GG and TP53 72Pro/Pro genotypes being 10 (95% confidence interval 0.39-255.55).