Dichlorodiphenyltrichloroethane technical mixture regulates cell cycle and apoptosis genes through the activation of CAR and ERα in mouse livers

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

“…Studies using CAR-null mice have demonstrated that CAR activation is an essential requirement for liver tumour development via a nongenotoxic mode of action, apparently through the induction of cell proliferation and suppression of apoptosis (Yamamoto et al, 2004;Huang et al, 2005). Indeed, CAR activation is associated with the increased or decreased expression of a large set of cell cycle regulators, including Cyclin D1, Mdm2, cMyc, Gadd45β, Cdkn1a, and others (Ledda- Columbano et al, 2003;Columbano et al, 2005;Yamamoto and Negishi, 2008;Yamamoto et al, 2010;Huang et al, 2005;Blanco-Bose et al, 2008;Kazantseva et al, 2013Kazantseva et al, , 2014. The promitogenic protein cMyc has been implicated in various aspects of liver proliferation.…”

“…Preparation of whole liver extracts and nuclear proteins from mouse livers and western blot analysis was performed as described previously (Kazantseva et al, 2013). Sixty micrograms of proteins was separated by SDS-PAGE, transferred onto nitrocellulose membranes, and exposed to the indicated antibodies before being visualised by Luminata Crescendo Western HRP Substrate (Millipore, MA, USA).…”

Stat3 is a candidate epigenetic biomarker of perinatal Bisphenol A exposure associated with murine hepatic tumors with implications for human health

“…We chose translationally-relevant candidate genes with functional links to hepatocellular carcinoma (HCC) for analysis based on expression changes reported in the literature in both rodent and human liver tumors. Three candidate genes were chosen: estrogen receptor a (Esr1/ESR1) [13][14][15][16] ; interleukin 6 signal transducer (Il6st/IL6ST), [17][18][19][20] also known as gp130; and signal transducer and activator of transcription 3 (Stat3/STAT3). 18,21 These candidate genes are functionally linked.…”

The effect of acute dichlorodiphenyltrichloroethane exposure on hypermethylation status and down‐regulation of p53 and p16INK4a genes in rat liver

“…Recently, Kazantseva et al, have demonstrated that a single dose of mixture DDT (85% p,p ' ‐DDT and 15% o,p'‐DDT) regulates cell cycle and apoptosis genes through the activation of CAR (constitutive active/androstane receptor) and ERα (estrogen receptor alpha) in mouse livers. Moreover, increases in cell cycle progression and anti‐apoptosis proteins were accompanied by a decrease in p53 content and its transcriptional activity (Kazantseva et al, ).…”

“…It has been established that onset of cancer, including hepatocarcinogenesis is related to the loss of control of normal apoptosis and the disturbance of equilibrium between cellular apoptosis and proliferation (Liu et al, 2009;Kutanzi et al, 2010). Indeed, also the DDT-induced cell proliferation and inhibition of apoptosis have been shown in the rodent liver and the alterations in the relevant genes expression were observed (Kostka et al, 2000;Harada et al, 2003;Frigo et al, 2004;Kazantseva et al, 2013). Hence, transcriptional inactivation of the cell-cycle-related genes, such as p53 and p16 INK4a (p16), may be crucial for tumor development.…”