Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.

ABSTRACT: The constitutive active/androstane receptor (CAR) mediates responses to the nongenotoxic rodent liver tumor promoter phenobarbital (PB), including certain gene expression changes, hepatomegaly, and tumor formation. Aberrant DNA methylation represents epigenetic events that can play multiple roles in tumorigenesis. Previously, 146 unique PB-induced regions of altered DNA methylation (RAMs) were observed in liver tumor-susceptible CAR wild-type (WT) mice (in 23 weeks, precancerous tissue, and 32 weeks, tumor tissue), as compared to the resistant knockout (KO). We believe that at least some of these might be key for tumorigenesis. In the current study, cloning and annotation of a subset (82%) of the unique RAMs revealed 47 genes exhibiting altered methylation; 17 are already implicated in can

SUBMITTER: Phillips JM 

PROVIDER: S-EPMC2664694 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature