title: 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 AktDD (T308D, S473D) resulted in increased phosphorylation of GSK3beta, 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 AktDD (MCF-7 AktDD) compared to vector control cells (MCF-7 vec). MCF-7 AktDD 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 AktDD cells as compared to MCF-7 vec cells. Overexpression of AktDD also attenuated tamoxifen-mediated apoptosis. These results suggest that Akt could confer resistance to anti-estrogen mediated cell death and inhibition of proliferation.
authors.affiliation: Department of Cancer Biology, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6307, USA.
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D013629:Tamoxifen / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D013629:Tamoxifen; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt