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Aberrant expression of fibroblast growth factor receptor‐1 in prostate epithelial cells allows induction of promatrilysin expression by fibroblast growth factors
Author(s) -
Udayakumar T.S.,
Klein Russell D.,
Maliner M. Suzanne,
Nagle Raymond B.,
Bowden G.T.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1023>3.0.co;2-w
Subject(s) - lncap , fibroblast growth factor receptor , prostate cancer , stromal cell , cancer research , fibroblast growth factor , biology , transfection , fgf10 , fibroblast growth factor receptor 3 , fibroblast growth factor receptor 4 , cell culture , receptor , cancer , genetics , biochemistry
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. © 2001 Wiley‐Liss, Inc.