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These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.

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BACKGROUND. Growth and development of the prostate are androgen-dependent. Keratinocyte growth factor (KGF), widely expressed by mesenchymal cells, is thought to act like an andromedin between stroma and epithelium of the prostate. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its relationship to androgen receptor (AR). METHODS. Normal (n = 13), benign hyperplastic (n = 5), and neoplastic (n = 14) human prostate tissues as well as cultured epithelial and stromal cells were analyzed using polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. RESULTS. Reverse transcriptase polymerase chain reaction and Western blotting showed KGF expression in stromal cultured cells of the normal prostate but not in epithelial cells. Using immunohistochemistry, KGF was found to be localized in fibroblasts and smooth muscle cells, independent of prostate disease. There was KGF expression in epithelial cells of BPH and prostate cancer. Human androgen receptor was uniformly expressed in the same secretory glandular cells that were positive for KGF in BPH and prostate cancer. CONCLUSIONS. Our results provide evidence that KGF is a stromal-derived mediator, recently shown to act in a paracrine manner in normal prostate but now detected in epithelial cells in prostate cancer and BPH. These findings support the hypothesis that KGF might act as an autocrine factor in prostate cancer and BPH.