title: The PI3 kinase-Akt pathway mediates Wnt3a-induced proliferation.
abstract: Wnt3a activates proliferation of fibroblasts cells via activation of both extracellular signal-regulated kinase (ERK) and Wnt/beta-catenin signaling pathways. In this study, we show that the phosphatidyl inositol 3 kinases (PI3K)-Akt pathway is also involved in the Wnt3a-induced proliferation. Akt was activated within 30 min by Wnt3a in NIH3T3 cells. By Wnt3a treatment, activated Akt was transiently accumulated in nucleus although beta-catenin was accumulated in the nucleus of cells in a prolonged manner. The Wnt3a-induced Akt activation was not affected by siRNA-mediated reduction of beta-catenin, indicating that Wnt3a-induced Akt activation may occur independently of beta-catenin. The Wnt3a-induced Akt activation was abolished by pre-treatment with PI3K inhibitor, LY294002 and Wortmanin, but not by MEK inhibitor, U0126, indicating that Wnt3a activates Akt via PI3K. The growth and proliferation induced by Wnt3a were blocked by treatments of the PI3K inhibitors. Furthermore, Wnt3a-induced proliferation was blocked by Akt siRNA. These results reveal that the PI3K-Akt pathway mediates the Wnt3a-induced growth and proliferation of NIH3T3 cells.
authors.affiliation: Department of Biotechnology, National Research Laboratory of Molecular Complex Control, Seoul, South Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Won-Jeong
authors.initials: WJ
authors.lastname: Lee
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D007739:L Cells; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism / Q000494:pharmacology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse