PI3K/Akt signaling regulates p271kipl expression via Skp2 in PC3 and DU145 prostate cancer cells, but is not a major factor in p271kipl regulation in LNCaP and PC346 cells

BACKGROUND. We compared the involvement of PI3K/PTEN/Akt signaling in the regulation of the cell-cycle regulator p27(kip1) and investigated the mechanism of PI3K/PTEN/Akt modulation of P27(kip1) in the prostate cancer cell lines LNCaP, PC346, PC3, and DU145. METHODS. PI3K/PTEN/Akt signaling was manipulated by wortmannin or specific siRTNA. The effects on PI3K/Akt downstream effectors and p27(kip1) expression were monitored on RNA and protein levels. RESULTS. PI3K/Akt inhibition in LNCaP and PC346 cells hardly affected p27(kip1) expression. As shown in LNCaP cells, P27(kip1) expression inversely correlated with Skp2 expression, but Skp2 was not regulated by Akt. Blocking PI3K/Akt signaling in PC3 cells resulted in decreased Skp2 protein expression and increased p27(kip1). Downregulation of PTEN in DU145 cells also showed PTEN/Akt-dependent regulation of Skp2 and p27(kip1). CONCLUSIONS. In PC3 and DU145 cells, Skp2 is the main determinant in the PI3K/Akt-dependent regulation of p27(kip1). In LNCaP and PC346 cells, PI3K/Akt signaling is not a major factor in P27(kip1) regulation.