Aberrant expression of fibroblast growth factor receptor-1 in prostate epithelial cells allows induction of promatrilysin expression by fibroblast growth factors

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, and there is evidence that they play a role in turner cell growth, invasion an d metastasis, Matrilysin (MMP-7) is over-expressed in prostate cancer cells and increases prostate cancer cell invasion. Prostate stromal fibroblasts secrete a factor(s), including fibroblast growth factor-1 (FGF-1), which in duces promatrilysin expression in the prostate carcinoma cell line LNCaP bu t not in normal prostate epithelial cells (PrECs). Since FGF-1 is present i n the prostate, an altered sensitivity to FGF-1 might explain the upregulat ion of matrilysin expression in prostate cancer cells compared to normal pr ostate epithelium. FGF receptor-1 (FGFR-1) is not normally expressed by nor mal prostate epithelial cells; however, aberrant expression of this recepto r has been reported in prostate cancer cells, including the LNCaP cell line . We hypothesized that aberrant expression of FGFR-1 in PrECs would render them sensitive to induction of promatrilysin expression by recombinant FGF- 1. To test this hypothesis, we transiently transfected PrECs with an FGFR-1 expression vector, which resulted in over-expression of FGFR-1 protein in approximately 40% of cells, POP-I increased promatrilysin expression in FGF R-1-transfected PrECs 4-fold over mock-transfected cells, and this inductio n was inhibited by a specific FGFR-1 inhibitor, SU5402, and by co-expressio n of a dominant negative FGFR-1 protein. Our results demonstrate that aberr ant FGFR-1 expression, an epigenetic phenomenon that has been associated wi th prostate cancer progression, allows induction of promatrilysin expressio n by FGF-1 in PrECs. (C) 2001 Wiley-Liss, Inc.