Characterization of flbroblast growth factor receptors in human prostate cancer
Leung HY., Gray L., Collins AT., Robson CN., Neal DE.
Introduction: Fibroblast growth factor receptors (FGFRs) mediate the activities of fibroblast growth factors (FGFs). Four human FGFR genes (FGFR1-4) have been identified, with FGFR1-3 capable of generating isoforms with different FGF binding. For instance, the IIIb and IIIc isoforms of FGFR2 bind specifically to KGF and bFGF. respectively. Materials and methods: FGFR expression in 17 cases of prostate cancer and six cases of BPH were studied using RTPCR. The IIIb isoform of FGFR1 and 2 was further characterized in an in vitro model of cultured cells, including DU145 and LNCaP cells, transformed epithelial cells (PNT1a) and primary cultured prostatic cells. The functional significance of FGFR was assessed by a proliferation assay using exogenous KGF and bFGF. Results: All 17 prostate cancers were positive for FGFR1-IIIb mRNA. but none expressed FGFR1-IIIc. In the BPH samples, FGFR1-IIIb transcripts were detected in four of six cases. FGFR2-IIIb expression was detected in 12 of 17 cases of prostate cancer (six at high levels) and five of six cases of BPH, while FGFR2-IIIc expression was present in 10 of 17 tumours (one at a high level) but absent in all six BPH samples. The expressions of the alternative exons IIIb and IIIc at high levels were mutually exclusive. FGFR3 expression was not detected in BPH and prostate cancer by Northern blotting. KGF but not bFGF had a mitogenic effect of up to 100% on cultured prostatic epithelial cells. FGFR1-IIIb expression was detected in LNCaP. PNT1a and cultured epithelial cells, but was absent in DU145 and cultured stromal cells. FGFR2-IIIb was expressed in DU145 and both cultured epithelial and stromal cells. Conclusion: Splice variants of FGFR1 and 2 are expressed in proslate cancer, and the expressions of FGFR1-IIIb and FGFR2-IIIc isoforms were up-regulated in prostate cancer. © 1997 British Journal of Urology.