title: CYR61 controls p53 and NF-κB 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-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.
authors.affiliation: Department of Obstetrics and Gynecology, Gachon University Gil Hospital, Guwol-Dong, Namdong-Gu, Inchen, Republic of Korea.
authors.forename: Kwang-Beom
authors.initials: KB
authors.lastname: Lee
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Byun
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Chan-Yong
authors.initials: CY
authors.lastname: Park
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D016190:Carboplatin; D055515:Cysteine-Rich Protein 61; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; C501848:CCN1 protein, human; C495901:TP53 protein, human; C546842:MTOR protein, human