title: Fibroblast growth factor 17 is over-expressed in human prostate cancer.
abstract: Over-expression of fibroblast growth factor 8 (FGF8) in human prostate cancer is associated with clinically aggressive disease. Among different members of the FGF family, FGF17 and FGF8 share high sequence homology and have similar patterns of expression during embryogenesis. In this study, the clinical significance of FGF17 expression and its in vitro function in prostate cancer cells were tested. Forty resected prostate specimens from patients with benign prostatic hyperplasia (BPH, n = 12) and prostate cancer (CaP, n = 28; Gleason sum scores 3-10) were studied using semi-quantitative RT-PCR. In addition, 85 cases of CaP (Gleason sum scores 5-9) and 20 cases of BPH were examined using immunohistochemistry and findings were correlated with clinical parameters. In vitro experiments using prostate cancer cell lines examined the functional significance of FGF17 in prostate cancer. These studies revealed a significant linear correlation between increasing Gleason sum scores and FGF17 expression using both immunohistochemistry (p < 0.0001, rho = 0.99) and RT-PCR (p = 0.008, rho = 0.99). Immunohistochemistry demonstrated upregulation of FGF17 in CaP compared with BPH (p < 0.0001) and, when comparing high-grade CaP (Gleason sum score 7-10) with BPH, RT-PCR showed a fourfold upregulation of FGF17 mRNA expression (p < 0.0001). Men with tumours displaying high levels of FGF17 expression had a worse outcome on survival analysis (p = 0.044) and a higher risk of progression with metastases (p < 0.0001). Proliferation assays showed low-dose recombinant (r) FGF17 (1 ng/ml) to be a more potent mitogen than rFGF1 and rFGF8 in prostate cancer cell lines (LNCaP, DU145, and PC3M) (p < 0.001). Furthermore, FGF8 was shown to induce expression of FGF17 in these cell lines. These data support a role for FGF17, and a model of co-expression of multiple FGFs, with FGF17 as a potential mediator of FGF8 function, in human prostate carcinogenesis.
authors.affiliation: Urology Research Group, Northern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne, UK. rakeshheer@hotmail.com
authors.forename: R
authors.initials: R
authors.lastname: Heer
authors.forename: D
authors.initials: D
authors.lastname: Douglas
authors.forename: M E
authors.initials: ME
authors.lastname: Mathers
authors.forename: C N
authors.initials: CN
authors.lastname: Robson
authors.forename: H Y
authors.initials: HY
authors.lastname: Leung
mesh_terms: D015153:Blotting, Western / Q000379:methods; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008934:Mitogens / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: C484724:FGF17 protein, human; C496456:FGF8 protein, human; D008934:Mitogens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors