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

Int J Cancer. 2001 Jan 15;91(2):187-92. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1023>3.3.co;2-n.

Abstract

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, and there is evidence that they play a role in tumor cell growth, invasion and 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 induces promatrilysin expression in the prostate carcinoma cell line LNCaP but not in normal prostate epithelial cells (PrECs). Since FGF-1 is present in the prostate, an altered sensitivity to FGF-1 might explain the up-regulation of matrilysin expression in prostate cancer cells compared to normal prostate epithelium. FGF receptor-1 (FGFR-1) is not normally expressed by normal prostate epithelial cells; however, aberrant expression of this receptor 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. FGF-1 increased promatrilysin expression in FGFR-1-transfected PrECs 4-fold over mock-transfected cells, and this induction was inhibited by a specific FGFR-1 inhibitor, SU5402, and by co-expression of a dominant negative FGFR-1 protein. Our results demonstrate that aberrant FGFR-1 expression, an epigenetic phenomenon that has been associated with prostate cancer progression, allows induction of promatrilysin expression by FGF-1 in PrECs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dimerization
  • Enzyme Precursors / biosynthesis*
  • Epithelial Cells / chemistry
  • Fibroblast Growth Factors / pharmacology*
  • Humans
  • Male
  • Metalloendopeptidases / biosynthesis*
  • Prostate / chemistry*
  • Pyrroles / pharmacology
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / analysis*
  • Receptors, Fibroblast Growth Factor / chemistry
  • Receptors, Fibroblast Growth Factor / physiology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Enzyme Precursors
  • Pyrroles
  • Receptors, Fibroblast Growth Factor
  • SU 5402
  • Fibroblast Growth Factors
  • FGFR1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Metalloendopeptidases
  • promatrilysin