Down-regulation of (IIIb) and (IIIc) isoforms of fibroblast growth factor receptor 2 (FGFR2) is associated with malignant progression in human prostate.

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) have a critical function in the cellular stroma/epithelium interaction for the development and homeostasis of human prostate. Imbalance in expression of these factors is associated with malignancy in several cancers. To quantify the expression of fibroblast growth factor receptor isoforms FGFR2(IIIb), FGFR2(IIIc), FGFR1(IIIc), and fibroblast growth factors FGF2 and FGF7 in normal and tumoral human prostate tissues, and human prostatic epithelial cell lines, we used quantitative real-time polymerase chain reaction. The expression of FGFR2(IIIb) mRNA is down-regulated in 60% of the tumors studied (P < 0.0001). Furthermore, FGFR2(IIIb) is significantly reduced in androgen-independent tumors (AI) compared with androgen-responsive tumors (AD) (P = 0.02). A significant reduction in FGFR2(IIIc) expression is also observed in 80% of tumors (P = 0.001). However, unlike FGFR2(IIIb), the down-regulation of FGFR2(IIIc) is not related to the androgen-independent status (P = 0.09). On the other hand, neither FGFR1(IIIc) nor FGF2 and FGF7 have shown any significant variation in expression between normal and cancerous specimens. These findings propose that decreased expression of not only FGFR2(IIIb) but also FGFR2(IIIc) isoforms may be a critical step in prostate cancer progression and furthermore suggest that FGFR2(IIIb) expression could be used as a marker for prostate cancer evolution from androgen-dependent to androgen-independent status.