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.
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.
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.
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).
Ultimately, P53 (N340Q/L344R) accerlerates the growth of liver cancer cells Hep3B by activating telomerase and prolonging telomere through the cascade of P53 (N340Q/L344R)-CUDR-PKM2-pH3T11- (H3K9me1-HP1α)-Pim1- (TERT-HOTAIR-TERRA).
The mutation Arg114Gly was predicted bioinformatically to affect Nogo-66 dimensional structure of Nogo-C. Our previous works also had indicated that mutant Nogo-C promoted liver cancer cell line apoptosis and resulted in molecular marker of HCC p53 gene transfer from nucleus to cytoplast.
Aflatoxin may increase the proportion of p53 mutations by causing a single mutation, the codon 249 G > T transversion, thus explaining some of the excess liver cancer associated with aflatoxin exposure.
This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer.
Mutations in p53 have successfully been used to establish links between dietary aflatoxin exposure and liver cancer, exposure to ultraviolet light and skin cancer, smoking and cancers of the lung and bladder, and vinyl chloride exposure and liver cancer.
Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers.
In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent.
Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues.
The purpose of the current investigation was to define the prevalence of genetic alterations in p16 and beta-catenin in NNK-induced rat liver cancer to determine if the molecular mechanisms seen in human tumors are the same in this animal model.
Here, we analyzed in preneoplastic and neoplastic livers from Fisher 344 and Brown Norway rats, possessing different genetic predisposition to HCC, in transforming growth factor-alpha (TGF-alpha) and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (i) iNOS function and interactions with nuclear factor-kB (NF-kB) and Ha-RAS/extracellular signal-regulated kinase (ERK) during hepatocarcinogenesis; (ii) influence of genetic predisposition to liver cancer on these pathways and role of these cascades in determining a susceptible or resistant phenotype and (iii) iNOS prognostic value in human HCC.
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.