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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Carboplatin / antagonists & inhibitors
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Carboplatin / pharmacology*
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Cell Line, Tumor
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Cysteine-Rich Protein 61 / biosynthesis
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Cysteine-Rich Protein 61 / genetics
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Cysteine-Rich Protein 61 / metabolism*
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Female
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Humans
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NF-kappa B / biosynthesis*
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism*
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases / metabolism
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Transfection
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Tumor Suppressor Protein p53 / biosynthesis*
Substances
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CCN1 protein, human
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Cysteine-Rich Protein 61
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NF-kappa B
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Phosphoinositide-3 Kinase Inhibitors
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TP53 protein, human
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Tumor Suppressor Protein p53
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Carboplatin
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases