KMID : 0578320120340030323
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Molecules and Cells 2012 Volume.34 No. 3 p.323 ~ p.328
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Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells
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Kim Min-Jung
Sun Yuan-Jie Yang Hai-Jie Kim Nam-Ho Jeon Sung-Ho Huh Sung-Oh
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Abstract
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Lysophosphatidic acid (LPA) is a lipid growth factor that induces proliferation of fibroblasts by activating the cAMP response element binding protein (CREB). Here, we further investigated whether LPA induces proliferation of P19 cells, a line of pluripotent embryonic carcinoma cells. 5?-Bromo-2-deoxyuridine incorporation and cell viability assays showed that LPA stimulated proliferation of P19 cells. Immunoblot experiments with P19 cells revealed that the mitogen activated protein kinases, including p-ERK, p38, pAKT, glycogen synthase kinase 3?, and CREB were phosphorylated by treatment with 10 ?M LPA. LPA-indu-ced phosphorylation of CREB was efficiently blocked by U0126 and H89, inhibitors of the MAP kinases ERK1/2 and mitogen- and stress-activated protein kinase 1, respec-tively. Involvement of cyclin D1 in LPA-induced P19 cell proliferation was verified by immunoblot analysis in combination with pharmacological inhibitor treatment. Furthermore, LPA up-regulated CRE-harboring cyclin D1 promoter activity, suggesting that CREB and cyclin D1 play significant roles in LPA-induced proliferation of P19 embryonic carcinoma cells.
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KEYWORD
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cAMP response element binding protein (CREB), cyclin D1, lysophosphatidic acid, P19 embryonic carcinoma cell, proliferation
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