Casein Kinase I epsilon positively regulates the Akt pathway in breast cancer cell lines.

The Akt pathway is very important in both development and cancer. Here we show that, expression of Casein Kinase I epsilon (CKIepsilon) causes up-regulation of the Akt pathway despite normal protein expression of the pathway inhibitor phosphate and tensin homologue deleted on chromosome ten (PTEN). Conversely, we show that a CKIepsilon/delta-specific inhibitor can inhibit Akt phosphorylation at both Thr308 and Ser473 and drastically reduce phosphorylation of the Akt target Glycogen Synthase Kinase 3beta (GSK3beta). These conclusions were confirmed between MCF7 cells transiently transfected with CKIepsilon and Hs578T cells which already express endogenous CKIepsilon. The results suggest that CKIepsilon is a new positive regulator of the Akt pathway. Here we propose that, rather than inhibiting PTEN function, CKIepsilon positively regulates Akt possibly by inhibiting Protein Phosphatase 2A (PP2A).