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Mol. Cells 2012; 34(3): 323-328

Published online July 27, 2012

https://doi.org/10.1007/s10059-012-0163-6

© The Korean Society for Molecular and Cellular Biology

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Min-Jung Kim, Yuanjie Sun, Haijie Yang, Nam-Ho Kim, Sung Ho Jeon1, and Sung-Oh Huh*

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea, 1Department of Life Science, Hallym University, Chuncheon 200-702, Korea

Correspondence to : *Correspondence: s0huh@hallym.ac.kr

Received: June 19, 2012; Accepted: June 25, 2012

Abstract

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.

Keywords cAMP response element binding protein (CREB), cyclin D1, lysophosphatidic acid, P19 embryonic carcinoma cell, proliferation

Article

Research Article

Mol. Cells 2012; 34(3): 323-328

Published online September 30, 2012 https://doi.org/10.1007/s10059-012-0163-6

Copyright © The Korean Society for Molecular and Cellular Biology.

Involvement of the cAMP Response Element Binding Protein, CREB, and Cyclin D1 in LPA-Induced Proliferation of P19 Embryonic Carcinoma Cells

Min-Jung Kim, Yuanjie Sun, Haijie Yang, Nam-Ho Kim, Sung Ho Jeon1, and Sung-Oh Huh*

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea, 1Department of Life Science, Hallym University, Chuncheon 200-702, Korea

Correspondence to:*Correspondence: s0huh@hallym.ac.kr

Received: June 19, 2012; Accepted: June 25, 2012

Abstract

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.

Keywords: cAMP response element binding protein (CREB), cyclin D1, lysophosphatidic acid, P19 embryonic carcinoma cell, proliferation

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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