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Lookup NU author(s): Bharat Gowardhan, David Douglas, Dr Marie Mathers, Dr Arthur Mckie, Dr Stuart McCracken, Professor Craig Robson, Professor Hing Leung
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Overexpression of fibroblast growth factors (FGFs) has been implicated in prostate carcinogenesis, FGFs function via their high-affinity interactions with receptor tyrosine kinases, FGFR1-4. Expression of FGFR1 and FGFR2 in prostate cancer (CaP) was not found to be associated with clinical parameters. In this report, we further investigated for abnormal FGFR expression in prostate cancer and explore their significance as a potential target for therapy. The expression levels of FGFR3 and FGFR4 in CaP were examined and corroborated to clinical parameters. FGFR3 immunoreactivity in benign prostatic hyperplasia (BPH) and CaP (n = 26 and 57, respectively) had similar intensity and pattern. Overall, FGFR4 expression was significantly upregulated in CaP when compared to BPH. A significant positive correlation between FGFR4 expression and Gleason score was noted: Gleason score 7-10 tumours compared to BPH (P < 0.0001, Fisher's exact test), Gleason score 4-6 tumours compared to BPH (P < 0.0004), and Gleason 7-10 compared to Gleason 4-6 tumours (P<0.005). FGFR4 overexpression was associated with an unfavourable outcome with decreased disease-specific survival (P<0.04, log rank test). FGF-induced signalling is targeted using soluble FGF receptor (sFGFR), potent inhibitor of FGFR function. We have previously shown that sFGFR expression via a replication-deficient adenoviral vector (AdIIIcRI) suppresses in vitro FGF-induced signalling and function in human CaP DU145 cells. We tested the significance of inhibiting FGF function along with conventional therapeutic modalities in CaP, and confirmed synergistic effects on in vitro cell growth (proliferation and colony formation) by combining sFGFR expression and treatment with either Paclitaxel (Taxol®) or γ-irradiation. In summary, our data support the model of FGF system as valid target for therapy in CaP. © 2005 Cancer Research UK.
Author(s): Gowardhan B, Douglas DA, Mathers ME, Mckie AB, McCracken SRC, Robson CN, Leung HY
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2005
Volume: 92
Issue: 2
Pages: 320-327
Print publication date: 31/01/2005
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
URL: http://dx.doi.org/10.1038/sj.bjc.6602274
DOI: 10.1038/sj.bjc.6602274
PubMed id: 15655558
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