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Expression of active Akt protects against tamoxifen‐induced apoptosis in MCF‐7 Cells
Author(s) -
Shin Incheol,
Arteaga Carlos L.
Publication year - 2006
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540601001681
Subject(s) - mcf 7 , protein kinase b , apoptosis , estrogen receptor , tamoxifen , cell growth , cancer cell , cancer research , phosphorylation , cell culture , chemistry , biology , microbiology and biotechnology , breast cancer , cancer , human breast , biochemistry , genetics
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 GSK3β, 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.iubmb Life, 58: 664 ‐ 669, 2006