Bedeutung der Östrogene und ihrer Rezeptoren für die Entstehung und Progression des Prostatakarzinoms

The recent discovery of the estrogen receptors alpha and beta (ER, ER) and the progesterone receptor (PR) in human prostate tissue offers new insights into the role of estrogens and their receptors in prostate cancer development and tumor progression. The differentiation compartment of the prostatic epithelium (secretory luminal cells) expresses high levels of ER, while the ER is restricted to the proliferation compartment (basal cells). In high grade prostatic intraepithelial neoplasia (HGPIN), ER gene expression extends to luminal cells and thus may mediate cancerogenic effects of estrogens on the dysplastic epithelium. Conversely, the ER is downregulated in HGPIN indicating that the chemopreventive effects of phytoestrogens mediated by the ER are partially lost. Irrespective of grades and stages, prostate cancer retains high levels of the ER which is partially lost in androgen-insensitive stages of the disease. In contrast with breast cancer, the presence of the ER a nd the PR is a late event in prostate cancer progression. At least 30% of metastatic and androgen-insensitive tumors express high levels of the PR indicating that these tumors harbor a functional ER. The antiestrogen Raloxifene has growth-inhibitory effects on androgen-insensitive prostate cancer cells in vitro and induces the apoptotic cell death in a dose-dependent fashion. These data provide a rational for clinical trials to study the efficiency of antiestrogens in the medical treatment of advanced prostate cancer.