
<ArticleTitle><prot>Keratinocyte growth factor</prot> activates <prot>p38</prot> MAPK to induce stress fibre formation in human prostate DU145 cells.</ArticleTitle>
<AbstractText>FGF7/<prot>Keratinocyte growth factor</prot> (<prot>KGF</prot>) regulates the differentiation and development of the prostate epithelium, while over-expression of <prot>FGF8</prot> and <prot>FGF1</prot> are implicated in carcinogenesis of the prostate. We tested the hypothesis that different members of the FGF family function through different signalling molecules. In prostate DU145 cells, both <prot>FGF1</prot> and <prot>FGF2</prot> activated <prot>ERK1/2</prot> potently and <prot>p38</prot> moderately. <prot>KGF</prot> was however most efficient in inducing <prot>p38</prot> activities but had no effect on <prot>ERK1/2</prot> function. <prot>JNK</prot> and <prot>STAT</prot> activities were not induced by FGFs in prostate cells. In vitro expression of the transcription factors <prot>Elk-1</prot> and <prot>MEF2A</prot> (substrates for <prot>ERK1/2</prot> and <prot>p38</prot>, respectively) for functional quantification, confirmed the pattern of FGF-induced MAPK activations in COS-7 cells. Furthermore, <prot>KGF</prot> was more efficient than <prot>FGF1</prot> and <prot>FGF2</prot> in inducing actin stress fibres, and the specific <prot>p38</prot> inhibitor SB202190 completely abolished this in a dose-dependent manner. The <prot>MEK1/2</prot> inhibitor, U0126, had no effect on FGF-induced stress fibre formation. This study demonstrates the selective activation of MAPK family members by FGFs resulting in activation of transcription factors and stress fibre formation. As multiple FGFs are over-expressed in human prostate cancer, characterization of the distinct signalling pathway by FGFs may reveal new specific targets for therapy.</AbstractText>
