Immunolocalization of the keratinocyte growth factor in benign and neoplastic human prostate and its relation to androgen receptor

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 pro state. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its re lationship 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 blotti ng showed KGF expression in stromal cultured cells of the normal prostate b ut 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 c ancer. Human androgen receptor was uniformly expressed in the same secretor y glandular cells that were positive for KGF in BPH and prostate cancer. CONCLUSIONS. Our results provide evidence that KGF is a stromal-derived med iator, recently shown to act in a paracrine manner in normal prostate but n ow detected in epithelial cells in prostate cancer and BPH. These findings support the hypothesis that KGF might act as an autocrine factor in prostat e cancer and BPH. (C) 1999 Wiley-Liss, Inc.