Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1672415
- author
- Tarkkonen, Kati ; Ruohola, Johanna and Härkönen, Pirkko LU
- organization
- publishing date
- 2010
- 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
- pmid:20370578
- ISSN
- 0897-7194
- DOI
- 10.3109/08977191003745480
- language
- English
- LU publication?
- yes
- additional info
- Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:29.
- id
- e87334ff-36c8-4ff2-8158-a507c10da423 (old id 1672415)
- date added to LUP
- 2016-04-01 10:16:36
- date last changed
- 2022-01-25 21:39:21
@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}}, keywords = {{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}}, doi = {{10.3109/08977191003745480}}, volume = {{28}}, year = {{2010}}, }