Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the constitutive androstane receptor (CAR) resulting in rodent liver tumors.
The prevalence of tumors in Ctnnb1 KO mice was ∼7-fold higher than in wild-type mice, suggesting an enhancing effect of the gene KO on liver tumor development.
To test this hypothesis and determine whether the mouse Ahr gene acts as a tumor suppressor gene in vivo, we have examined the role of Ahr ablation in liver tumorigenesis induced by the genotoxic chemical diethylnitrosamine (DEN), a hepatic carcinogen that is not an AHR ligand.In mice given a single i.p. injection of DEN, AHR antagonized liver tumor formation and growth by regulating cell proliferation, inflammatory cytokine expression, and DNA damage, parameters which were significantly elevated in the livers of control and, more so, of DEN-exposed Ahr-/- mice.
Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.
The constitutive active/androstane receptor facilitates unique phenobarbital-induced expression changes of genes involved in key pathways in precancerous liver and liver tumors.
Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation.
In contrast, only three of 18 vinyl carbamate-induced liver tumors, one of 18 TCDD-induced liver tumors, and two of 22 spontaneous liver neoplasms had mutations in beta-catenin.
Transgenic mouse models in carcinogenesis: interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis.
The similarity in the patterns of global gene expression of Ha-ras and B-raf mutated liver tumors suggests that mutational activation of the 2 oncogenes results in activation of a common set of transcriptional regulators.
The incidence of KRAS2 mutations in human compared to mouse lung tumors differed significantly, as did the incidence of Hras and p53 gene mutations in human compared to mouse liver tumors.
A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ-protein (connexin 32) was employed to study GJ-protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2-acetylaminofluorene (AAF)/CCl4/AAF or induced by systemic administration of N-ethyl-N-hydroxyethylnitrosamine (EHEN).
Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen.