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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antineoplastic Agents, Down-Regulation, Estrogen Receptor beta, Gene Expression Regulation, Neoplastic, Genistein, Humans, Male, Prostate-Specific Antigen, Prostatic Neoplasms, Receptors, Androgen, Receptors, Estrogen, Tumor Cells, Cultured.
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Is androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells mediated by estrogen receptor beta? Context: Isoflavonoids are discussed for use in chemoprevention and treatment of prostate cancer. We investigated the potential of genistein to modulate androgen receptor (AR) expression and transcriptional activity in the human androgen-sensitive prostate cancer cell line LNCaP. AR expression at mRNA and protein level was analyzed by real-time RT-PCR and immunoblot, respectively. In conditioned media PSA was measured by a microparticle enzyme immunoassay (MEIA). Binding of genistein to the AR was tested in a radioligand-binding assay and reporter gene co-transfection assay was employed to investigate AR activity. Using concentrations of genistein that have been detected in sera of Asian men on regular soy-diet we found down-regulation of androgen receptor at both mRNA and protein level. The relative binding affinity to the AR was below 4% when compared to methyltrienologe (R1881) and there was no modulation of AR transcriptional activity by genistein concentrations up to 1 microM. We also demonstrated inhibition of PSA secretion after genistein treatment. As the anti-estrogen ICI 164 384 abolished the inhibitory effect of genistein and ER-beta, but not ER-alpha is expressed in LNCaP cells we postulate that the mechanism of genistein action on androgen receptor is mediated through ER-beta.
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Using physiological concentrations of genistein we showed AR down-regulation by genistein in prostate cancer cells occurring via ER-beta. This likely results in a modified response to hormonal stimuli and may help to explain the low incidence of prostate cancer in the Asian population. Final Decision: yes