Expression of active Akt protects against tamoxifen-induced apoptosis in MCF-7 cells

Abstract

We investigated the effect of constitutive active Akt expression on anti-proliferative and apoptotic effect of tamoxifen in MCF-7 human breast cancer cells. Forced expression of Akt(DD) (T308D, S473D) resulted in increased phosphorylation of GSK3 beta, a physiological substrate of Akt. When estrogen receptor (ER) mediated transcription was determined by luciferase assays, there was more than 2-fold increase in estradiol-dependent transcription in MCF-7 cells overexpressing Akt(DD) (MCF-7 Akt(DD)) compared to vector control cells (MCF-7 vec). MCF-7 Akt(DD) cells showed increased proliferation in a medium containing charcoal stripped serum supplemented with estradiol. When the cell cycle profiles were examined, there was an increase in S-phase and a reduction in G1 phase in MCF-7 Akt(DD) cells as compared to MCF-7 vec cells. Overexpression of Akt(DD) also attenuated tamoxifen-mediated apoptosis. These results suggest that Akt could confer resistance to anti-estrogen mediated cell death and inhibition of proliferation.