The connection of β-catenin and phenobarbital in murine hepatocarcinogenesis: a critical discussion of Awuah et al., PLoS ONE 7(6):e39771, 2012.

摘要

Phenobarbital (PB) is frequently used as a promoter of rodent liver tumors. The mechanisms by which PB exerts its tumor-promoting activity are still not fully understood, but the constitutive androstane receptor (CAR) and (3-catenin seem to be essentially involved: Experiments with Car knockout (KO) mice have proven that the presence of CAR is mandatory for PB-mediated tumor promotion (Yamamoto et al. 2004). In mice, PB selects for the outgrowth of hepatocellular tumors with activating mutations in the Ctnnbl gene, which encodes the transcription factor P-catenin (Aydinlik et al. 2001). Similar observations were made with the PB-like tumor promoter PCB153 (Strathmann et al. 2006). Furthermore, CAR and P-catenin interact in the regulation of enzyme induction and hepatocyte proliferation triggered by PB (Braeuning et al. 2009; Braeuning et al. 2011).