Effect of human umbilical cord blood derived CD34+ hematopoietic stem cell on the expression of Wnt4 and P53 genes in a rat model of hepatocellular carcinoma.
The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability.
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.
Collectively, our present results suggest that the abnormal cytoplasmic localization of p53 might contribute at least in part to the development of HBL.
It includes integration of hepatitis B virus (HBV) DNA, R249STP53 (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations related to vinyl chloride exposure, hepatocyte nuclear factor 1alpha (HNF1alpha) mutations associated to hepatocellular adenomas and adenomatosis polyposis coli (APC) germline mutations predisposing to hepatoblastomas.
Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (< 24 months vs. > or = 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid).
Our results suggest that, in contrast to the findings in HCCs in adults, TP53 gene aberrations are not involved in the development or progression of HBLs in children.
The findings suggest that particular environmental mutagens may be involved in mutagenesis of the p53 gene in some cases of hepatoblastomas and that p53 mutations at a specific site may play an important role in the genesis of this disease.
Finally, synthesis of p53 specific mRNA or protein in a HepG2 human hepatoblastoma cell line does not appear to be affected by gene expression and replication of human hepatitus B virus.