scholarly journals Phosphatidylinositol 3-kinase (PI3Kα)/AKT axis blockade with taselisib or ipatasertib enhances the efficacy of anti-microtubule drugs in human breast cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76479-76491 ◽  
Author(s):  
Floriana Morgillo ◽  
Carminia Maria Della Corte ◽  
Anna Diana ◽  
Concetta di Mauro ◽  
Vincenza Ciaramella ◽  
...  
2000 ◽  
Vol 166 (2) ◽  
pp. 329-338 ◽  
Author(s):  
B Dufourny ◽  
HA van Teeffelen ◽  
IH Hamelers ◽  
JS Sussenbach ◽  
PH Steenbergh

Treatment of quiescent MCF-7 human breast cancer cells with either the polypeptide growth factors insulin-like growth factor-I (IGF-I) or epidermal growth factor (EGF), the steroid hormone estradiol (E2) or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) results in increased steady-state levels of cyclin D1 mRNA and protein. Unexpectedly, this elevation of cyclin D1 expression by all of these agents is inhibited by the specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002. Since transcriptional activation of the cyclin D1 promoter by EGF, E2 and TPA is independent of PI3-K activity, these findings suggest a post-transcriptional role for PI3-K in the regulation of cyclin D1 expression. Here we show that inhibition of PI3-K by LY294002 decreases the half-life of the 4.5 kb cyclin D1 mRNA species. In contrast, the stability of the 1.5 kb cyclin D1 mRNA is not affected by PI3-K inhibition. PI3-K-mediated stabilization of mRNA is not a general phenomenon, since other rapidly regulated and unstable mRNAs, such as those encoding c-fos, c-jun and c-myc, are not stabilized upon activation of the PI3-K signaling pathway.


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