Journal
MOLECULES AND CELLS
Volume 34, Issue 3, Pages 323-328Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.1007/s10059-012-0163-6
Keywords
cAMP response element binding protein (CREB); cyclin D1; lysophosphatidic acid; P19 embryonic carcinoma cell; proliferation
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Funding
- Priority Research Centers and Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science, and Technology [2011-0030750, 2011-0003931]
- Hallym University Research Fund [HRF-2009-039]
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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 beta, and CREB were phosphorylated by treatment with 10 mu M LPA. LPA-induced 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, respectively. 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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