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Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells

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Author

  • Kati Tarkkonen
  • Johanna Ruohola
  • Pirkko Härkönen

Summary, in English

Expression of fibroblast growth factor 8 (FGF-8) is increased in several forms of hormonal cancer. It was previously shown to regulate expression of thrombospondin 1 (TSP-1), an inhibitor of angiogencsis, in S115 breast cancer cells. Here, we studied the FGF-8-activated signalling pathways mediating TSP-1 repression in S115 cells and in non-tumorigenic MCF10A cells. Inhibition of FGF receptors or of MEK1/2 and PI3K with specific inhibitors (PD173074, U0126 or LY294002, respectively) restored TSP-1 mRNA expression in the presence of FGF-8 in S115 cells. Furthermore, U0126 and LY294002 increased TSP-1 mRNA expression in S115 cells over-expressing FGF-8. In MCF10A cells, FGF-8 treatment also decreased TSP-1 expression and the effect was dependent on active MEK1/2. In conclusion, FGF-8 suppresses TSP-1 expression through two independent pathways, MEK1/2 and PI3K. Repression of Tsp-1 may be an important mechanism involved in induction of an angiogenic phenotype and growth of FGF-8-expressing breast cancer.

Publishing year

2010

Language

English

Pages

256-267

Publication/Series

Growth Factors

Volume

28

Issue

4

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Cancer and Oncology

Keywords

  • kinases
  • mitogen-activated
  • Fibroblast growth factors
  • breast cancer cells
  • angiogenesis
  • thrombospondin

Status

Published

ISBN/ISSN/Other

  • ISSN: 0897-7194