title: Caveolin-1 plays important role in EGF-induced migration and proliferation of mouse embryonic stem cells: involvement of PI3K/Akt and ERK.
abstract: The involvement of caveolin-1 in the regulation of embryonic stem (ES) cell growth by epidermal growth factor (EGF) is by no means clear cut. Thus we examined the relationship between EGF and caveolin-1 in mouse ES cell migration and proliferation. The results revealed that EGF increased Src, caveolin-1, focal adhesion kinase (FAK), Akt, and extracellular signal-regulated kinase-1/2 (ERK) phosphorylation levels. Especially, phosphorylation of caveolin-1 is attenuated by AG1478, herbimycin A (tyrosine kinase inhibitors), and pyrazolopyrimidine 2 (PP2, Src inhibitor) and EGF-induced ERK activation was blocked by PP2, methyl-beta-cyclodextrin (MbetaCD), caveolin-1 small interfering RNA (siRNA), LY-294002 [phosphoinositol-3 kinase inhibitor (PI3K)], and Akt inhibitor. In addition, EGF promoted the cell migration, which was attenuated by PP2, caveolin-1 siRNA, FAK siRNA, LY-294002, Akt inhibitor, and PD-98059. EGF also increased matrix metalloproteinase (MMP-2) expression levels and EGF-induced MMP2 expression was inhibited by caveolin-1 siRNA, FAK siRNA, LY-294002, Akt inhibitor, and PD-98059. Furthermore, EGF-induced increase of cell cycle proteins expression level and [3H]thymidine incorporation was blocked by MMP inhibitor. EGF also significantly increases [(3)H]thymidine incorporation and cell number, which were significantly blocked by AG 1478, PP2, MbetaCD, caveolin-1 siRNA, FAK siRNA, LY-294002, and PD-98059 (ERK inhibitor). EGF-induced increase of protooncogenes (c-fos, c-myc, and c-Jun) and cell cycle regulatory proteins (cyclin D1, CDK4, cyclin E, and CDK2) expression levels were also attenuated by caveolin-1 siRNA and FAK siRNA. In conclusion, these results demonstrated that EGF-induced DNA synthesis and cell migration are mediated by caveolin-1, which is activated by Src, FAK, PI3K/Akt, ERK, and MMP-2 signals in mouse ES cells.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Park
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*
chemical_list: D051242:Caveolin 1; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases