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Protein kinase Cepsilon is important for migration of neuroblastoma cells

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Author

Summary, in English

Background: Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility. Methods: PKC isoforms were downregulated with siRNA or modulated with activators and inhibitors. Migration was analyzed with scratch and transwell assays. Protein phosphorylation and expression levels were measured with Western blot. Results: Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced migration of SK-N-BE(2) C neuroblastoma cells. Treatment with the general protein kinase C (PKC) inhibitor GF109203X and the inhibitor of classical isoforms Go6976 inhibited migration while an inhibitor of PKC beta isoforms did not have an effect. Downregulation of PKC epsilon, but not of PKC alpha or PKC delta, with siRNA led to a suppression of both basal and TPA-stimulated migration. Experiments using PD98059 and LY294002, inhibitors of the Erk and phosphatidylinositol 3-kinase (PI3K) pathways, respectively, showed that PI3K is not necessary for TPA-induced migration. The Erk pathway might be involved in TPA-induced migration but not in migration driven by PKC epsilon. TPA induced phosphorylation of the PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS) which was suppressed by the PKC inhibitors. Treatment with siRNA oligonucleotides against different PKC isoforms before stimulation with TPA did not influence the phosphorylation of MARCKS. Conclusion: PKC epsilon is important for migration of SK-N-BE(2) C neuroblastoma cells. Neither the Erk pathway nor MARCKS are critical downstream targets of PKC epsilon but they may be involved in TPA-mediated migration.

Publishing year

2008

Language

English

Publication/Series

BMC Cancer

Volume

8

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1471-2407