High consumption of soybean products, such as phytoestrogens, has been hypothesized to contribute to a reduced incidence of prostate cancer in Southeast Asian people, although there have been inconsistent results among studies. Human LNCaP cells, extensively used as a model for androgen-dependent prostate tumor, express the androgen receptor (AR) mutant T877A promiscuously transactivated by estrogens and other ligands, which may further facilitate cancer progression. Here, for the first time to our knowledge, we demonstrate that genistein and quercetin, two phytoestrogens abundantly present in soybeans, activate either the AR mutant T877A in LNCaP or in transfected Chinese hamster ovary cells. This observation is supported by their capability to induce AR accumulation in the nuclear compartment of LNCaP together with mRNA down-regulation of the androgen target genes AR and PAP, and PSA up-regulation. Of interest, at concentrations eliciting transcriptional activity, both genistein and quercetin stimulate LNCaP cell growth, whereas at high levels, they become cytotoxic independently of AR expression, as ascertained in steroid receptor-negative Hela cells. The results of our study provide evidence that phytoestrogens may regulate several signaling processes in LNCaP cells; however, further studies are needed to assess their potential capability to restrain prostate tumor progression.
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|Titolo:||The mutant androgen receptor T877A mediates the proliferative but not the cytotoxic dose-dependent effects of genistein and quercetin on human LNCaP prostate cancer cells|
|Data di pubblicazione:||2002|
|Appare nelle tipologie:||1.1 Articolo in rivista|