Phosphatidylinositol-3 kinase-dependent activation of Akt does not correlate with either high mitogenicity or cell migration induced by FGF-1.

FGF-1 is a pleiotropic growth factor that regulates proliferation, migration and differentiation of target cells. In pathological situations FGF-1 could have oncogenic potential either due to its mitogenic activity or due to formation of new blood vessels. FGF-1 exogenously added to cells not only activates specific cell surface receptors, but also enters the cytosol and the cell nucleus. Although much data concerning FGF-1-induced signal transduction and translocation of externally added FGF-1 into the cells are available, it is difficult to discriminate between events leading to cell proliferation and to other cellular responses. For the purpose of this study, we used primary human fibroblasts (HFb) from skin in order to compare the biological effects of FGF-1 in these cells and in NIH/3t3 cells. In this paper, we show that FGF-1 is much less mitogenic for HFb than for NIH/3T3 cells, with maximal stimulation obtained at a concentration one order of magnitude higher than for NIH/3T3 cells. Despite that, FGF-1 activates Akt kinase in HFb at lower concentrations than in NIH/3T3 cells. This activation is PI3-kinase-dependent, which shows that P13-kinase is activated upstream of Akt kinase in human fibroblasts. MAP kinases are activated in both cell types in a similar manner, but in HFb cells the inhibition of PI3-kinase by inhibitor LY294002 leads to activation of MAP kinases, while in NIH/3T3 cells this effect does not occur. Translocation of externally added FGF-1 to the cytosol/nucleus of HFb cells is similarly efficient as in NIH/3T3 cells. Our results show, also, that activation of Akt in HFb cells does not correlate with migratory response, since these cells migrate very inefficiently in response to FGF-1.