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

T. S. Udayakumar, Russell D. Klein, M. Suzanne Maliner, Raymond B. Nagle, G. T. Bowden

Research output: Contribution to journalArticle

21 Scopus citations

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-I (FGF-I), which induces promatrilysin expression in the prostate carcinoma cell line LNCaP but not in normal prostate epithelial cells (PrECs). Since FGF-I is present in the prostate, an altered sensitivity to FGF-I might explain the up regulation of matrilysin expression in prostate cancer cells compared to normal prostate epithelium. FGF receptor-I (FGFR-I) 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-I in PrECs would render them sensitive to induction of promatrilysin expression by recombinant FGF-I. To test this hypothesis, we transiently transfected PrECs with an FGFR-I expression vector, which resulted in over-expression of FGFR-I protein in approximately 40% of cells. FGF-I increased promatrilysin expression in FGFR-I-transfected PrECs 4-fold over mock-transfected cells, and this induction was inhibited by a specific FGFR-I inhibitor, SU5402, and by co-expression of a dominant negative FGFR-I protein. Our results demonstrate that aberrant FGFR-I expression, an epigenetic phenomenon that has been associated with prostate cancer progression, allows induction of promatrilysin expression by FGF-I in PrECs.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalInternational Journal of Cancer
Volume91
Issue number2
DOIs
StatePublished - Jan 15 2001

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Keywords

  • Fibroblast growth factor
  • LNCaP
  • Matrilysin
  • PrEc
  • Prostate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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