FGF7 AND FGF2 ARE INCREASED IN BENIGN PROSTATIC HYPERPLASIA AND ARE ASSOCIATED WITH INCREASED PROLIFERATION

Abstract

Purpose To determine if overexpression of FGF7 and FGF2 occurs in benign prostatic hyperplasia (BPH) and if so, whether such overexpression is correlated with increased proliferation of epithelial and/or stromal cells. Materials and Methods The FGF7 and FGF2 content of protein extracts of normal peripheral zone, normal transition zone and hyperplastic prostatic tissues were determined by enzyme-linked immunoabsorption assay. Proliferation of epithelial and stromal cells was assessed by immunohistochemistry with anti-Ki67 antibodies on frozen sections of the same tissues used for protein extraction. The in vitro effects of FGF7 and FGF2 on proliferation were assessed by addition of recombinant growth factor to primary cultures of prostatic epithelial and stromal cells. Results We have found that both FGF7 and FGF2 are overexpressed in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF7 is a potent mitogen for epithelial cells in culture. Consistent with these in vitro effects, quantitative analysis of cellular proliferation by Ki67 immunohistochemistry revealed a strong correlation of epithelial proliferation with FGF7 content in BPH tissue, consistent with a key role for this growth factor in driving the abnormal epithelial proliferation in BPH. FGF2 is mitogenic for stromal cells in culture and there was a weaker correlation of FGF2 content with increased stromal proliferation. Conclusion Overexpression of FGF7 and FGF2 may play an important role in the abnormal cellular proliferation seen in benign prostatic hyperplasia.