Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions.
These data suggest that activation of prostate cancer cell growth through growth factor receptor expression may result in the activity of otherwise androgen-independent stromal growth factor signals such as FGF-7 under conditions of androgen ablation.
To assess whether mutations in the hot-spots of the fibroblast growth factor (FGF) receptor-2 gene (FGFR2, exons encoding the IIIa, IIIb, IIIc and transmembrane domain, TMD) are associated with the development of prostate cancer, as the IIIb variant is the specific receptor for FGF7/KGF, an androgen-inducible paracrine factor regulating prostatic growth.
To better define the role of FGF2 and FGF7 in human prostate cancer in vivo, we have quantified these two growth factors in clinically localized human prostate cancers and uninvolved prostate by ELISA and Western blotting and determined their localization by immunohistochemistry.
However, KGF, KGF-R, and EGF-R mRNA were not expressed by human fetal prostate; (2) human adult prostate (BPH tissues) showed mRNA transcripts for all growth factors and their receptors except KGF-R; (3) human BPH-1 cell lines expressed mRNA transcripts for TGF-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, EGF, and KGF-R, but not for EGF-R and KGF growth factors; (4) human primary prostate cancer cell line (ND-1) showed mRNA transcripts for all growth factors except EGF and KGF; and (5) human prostate cancer cell lines (LNCaP, DU-145, PC-3) expressed mRNA transcripts for all growth factors except KGF, which was absent in all cell lines.
In situ hybridization studies with digoxigenin-labeled oligonucleotides (anti-sense and sense controls) were employed to examine KGF and KGF receptor mRNA expression in prostate cancer.