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SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling.
- Source :
-
Endocrine-related cancer [Endocr Relat Cancer] 2010 May 18; Vol. 17 (2), pp. 525-38. Date of Electronic Publication: 2010 May 18 (Print Publication: 2010). - Publication Year :
- 2010
-
Abstract
- Fibroblast growth factor-2 (FGF-2) is highly expressed in prostate cancer. It promotes tumour progression through multiple pathways including those of signal transducers and activators of transcription factor 3 (STAT3), mitogen-activated protein kinases (MAPKs) and Akt. In previous studies, we have reported that STAT3 phosphorylation inversely correlates with suppressor of cytokine signalling-3 (SOCS-3) expression in prostate cancer cells. Recently, it has become evident that SOCS-3-negative regulation is not only limited to the interleukin-6 (IL-6) receptor. We hypothesised that SOCS-3 interferes with FGF signalling, thus influencing the outcome of its action in prostate cancer cells. For this purpose, we treated DU-145 and LNCaP-IL-6+ cells with increasing concentrations of FGF-2, and verified protein phosphorylation. In the presence of FGF-2, neither STAT3, STAT1, nor Akt could be phosphorylated. Solely the p44/p42 MAPK pathway was activated after FGF-2 stimulation. We show for the first time that SOCS-3 interferes with the FGF-2 signalling pathway by modulating p44 and p42 phosphorylation in prostate cancer cells. Decreased SOCS-3 protein expression results in increased MAPK phosphorylation, whereas SOCS-3 overexpression leads to a decreased cellular proliferation and migration. On the basis of the present results, we propose that SOCS-3 is a novel modulator of FGF-2-regulated cellular events in prostate cancer.
- Subjects :
- Carcinoma metabolism
Cell Line, Tumor
Dose-Response Relationship, Drug
Fibroblast Growth Factor 2 pharmacology
Flavonoids pharmacology
Humans
Interleukin-6 pharmacology
Male
Mitogen-Activated Protein Kinase 1 antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 metabolism
Phosphorylation drug effects
Prostatic Neoplasms metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins metabolism
Carcinoma pathology
Cell Movement drug effects
Cell Proliferation drug effects
Fibroblast Growth Factor 2 antagonists & inhibitors
MAP Kinase Signaling System drug effects
Prostatic Neoplasms pathology
Suppressor of Cytokine Signaling Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1479-6821
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrine-related cancer
- Publication Type :
- Academic Journal
- Accession number :
- 20335309
- Full Text :
- https://doi.org/10.1677/ERC-10-0007