CYR61 controls p53 and NF-kappa B expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells

Abstract

CYR61 over-expression promotes cell proliferation by inhibiting carboplatin-induced apoptosis, decreasing Bax expression, and increasing Bcl-xL, Mcl-1, and Bcl-2. At the same time, down-regulating p53 expression, while up-regulated NF-kappa B expression. Additionally, p21 and p53 promoter activities were reduced, while NF-kappa B and Bcl-2 activities increased. In parallel, CYR61-expressing cells, during carboplatin-induced apoptosis, resulted in an increase of Akt phosphorylation, while rapamycin-treated cells were not affected. Carboplatin effectively inhibited the activation of mTOR signaling cascade, which includes mTOR, 4E-BP1, p70S6K, HIF-1 alpha, and VEGF. These results provide evidence that CYR61 promotes cell proliferation and inhibits apoptosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.