Neue Einblicke in die Rolle der Östrogene und ihrer Rezeptoren im Prostatakarzinom

The present review gives a survey on the differential expression of estrogen receptors alpha and beta (ER, ER) and the progesterone receptor (PR) in human prostate tissue and discusses their potential implications for normal and abnormal prostatic growth. 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 and the progesterone receptor (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 apoptotic cell death in a dose-dependent fashion. These data provide a rationale for clinical trials to study the efficiency of antiestrogens in the medical treatment of advanced prostate cancer.