Akt-isoform specific inhibition of MDA-MB-231 Cell Proliferation

Abstract

To dissect the isoform-specific rolesAkt in breast cancer cells, constitutively active Akt isoforms were introduced into MDA-MB-231 cells. Both Akt1 and Akt2 efficiently inhibited the growth of MDA-MB-231 cells. Over-expression of Akt1 down-regulated ERK activity by inhibiting Ser 259 phosphorylation of c-Rafand subsequentdownstream signaling. Akt2 over-expression up-regulated the cell cycle inhibitor p27. Cycloheximide decay assaysthat Akt2 increased the stability and nuclear localization of p27, thus inhibiting the cyclin E-CDK2 complex. These resultssuggest that the inhibition of cell proliferation by Akt1 and Akt2 is mediated by isoform-specific mechanisms.