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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

Tarkkonen, Kati; Ruohola, Johanna and Härkönen, Pirkko LU (2010) In Growth Factors 28(4). p.256-267
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
kinases, mitogen-activated, Fibroblast growth factors, breast cancer cells, angiogenesis, thrombospondin
in
Growth Factors
volume
28
issue
4
pages
256 - 267
publisher
Taylor & Francis
external identifiers
  • wos:000281471800004
  • scopus:77957775196
ISSN
0897-7194
DOI
10.3109/08977191003745480
language
English
LU publication?
yes
id
e87334ff-36c8-4ff2-8158-a507c10da423 (old id 1672415)
date added to LUP
2010-09-23 13:45:56
date last changed
2018-05-29 12:23:27
@article{e87334ff-36c8-4ff2-8158-a507c10da423,
  abstract     = {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.},
  author       = {Tarkkonen, Kati and Ruohola, Johanna and Härkönen, Pirkko},
  issn         = {0897-7194},
  keyword      = {kinases,mitogen-activated,Fibroblast growth factors,breast cancer cells,angiogenesis,thrombospondin},
  language     = {eng},
  number       = {4},
  pages        = {256--267},
  publisher    = {Taylor & Francis},
  series       = {Growth Factors},
  title        = {Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells},
  url          = {http://dx.doi.org/10.3109/08977191003745480},
  volume       = {28},
  year         = {2010},
}