AKT mediates actinomycin D-induced p53 expression

• DOI: 10.18632/oncotarget.1328
• Publication Date: 2015-09-16T20:56:42Z
• Authors: Chih-Shou Chen; Dong-Ru Ho; Fei-Yun Chen; Chang-Rong Chen; Yu-De Ke; Jyan-Gwo Joseph Su
• Keywords: Wortmannin; LY294002

// Chih-Shou Chen 1 , Dong-Ru Ho Fei-Yun 2 Chang-Rong Yu-De Ke Jyan-Gwo Joseph Su Division of Urology, Department Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan, ROC Biochemical Science and Technology, National Chiayi University, 600, Correspondence: Su, email: Keywords : Actinomycin D, AKT, p53 Received August 28, 2013 Accepted January 11, 2014 Published Abstract At high cytotoxic concentrations, actinomycin D (ActD) blocks transcription, decreasing levels MDM2 thus causing stabilization. low cytostatic ActD causes ribosomal stress, which decreases activity, resulting in stabilization activation. can be used for p53-based cyclotherapy. We analyzed pathways mediating ActD-induced expression. Inhibitors (LY294002, wortmannin, deguelin) phosphatidylinositol 3-kinases (PI3K) but not inhibitors MEK1/2, JNK, p38-MAPK abolished the expression diverse cell types. RNA interference further supported these results. When AKT was downregulated by small hairpin RNA-AKTs, significantly decreased. caused phosphorylation at Ser473, indicating full activation AKT. The potential cancer therapy is discussed.