Differential 14-3-3σ DNA methylation and expression in c-myc- and activated H-ras-transformed cells under r- and K-selection

We cloned rat 14-3-3σ, a mediator of p53 tumor suppressor, as a target of K-selection. 14-3-3σ expression is suppressed with DNA methylation in breast cancers while its overexpression with hypomethylation is frequent in pancreatic cancers. These opposite findings were recapitulated through r- and K-selection of transformed rat embryo fibroblasts. 14-3-3σ expression was suppressed with DNA methylation after r-selection and the gene was overexpressed and demethylated in K-selected cells. 5-aza-2′-deoxycytidine recovered 14-3-3σ expression in r-selected cells. The presence of heterogeneous methylation patterns and expression levels before selection suggests that different 14-3-3σ expression levels play a role as a prerequisite for selection and clonal evolution.