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

• Published in: Cancer letters 2012-02, Vol.315 (1), p.86-95
• Main Authors: Lee, Kwang-Beom, Byun, Hyun-Jung, Park, Sung Ho, Park, Chan-Yong, Lee, Seung-Hoon, Rho, Seung Bae
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Carboplatin; Carboplatin - antagonists & inhibitors; Carboplatin - pharmacology; CCN1 (CYR61); Cell Line, Tumor; Cysteine-Rich Protein 61 - biosynthesis; Cysteine-Rich Protein 61 - genetics; Cysteine-Rich Protein 61 - metabolism; Female; Hematology, Oncology and Palliative Medicine; Humans; NF-kappa B - biosynthesis; NF-κB; Ovarian carcinoma cells; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; PI3K/Akt; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Transfection; Tumor Suppressor Protein p53 - biosynthesis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2011.10.016

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-κB expression. Additionally, p21 and p53 promoter activities were reduced, while NF-κB 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-1α, and VEGF. These results provide evidence that CYR61 promotes cell proliferation and inhibits apoptosis.