Session: MON 355-388-Sex Hormone Receptor Action & Reaction
Poster Board MON-370
In this study, we investigated whether such a disordered ligand-NR interaction observed in MCF7 cells also exists in other hormone-dependent cell line, human prostate cancer LNCaP cells.
Expression of PTHrP was suppressed and that of PSA was stimulated by vitamin D3, DHT, E2, dexamethasone and R5020 in LNCaP cells, respectively. Expression of both AR and VDR was much higher than that of GR or PR, while the amounts of ERa and ERb were negligible in these cells. Interestingly, knockdown experiments by using siRNA for AR, but not for other NRs, revealed that suppression of PTHrP and stimulation of PSA gene expression by all the above steroid hormones were similarly canceled out. It is well known that the AR gene in LNCaP cells has a point mutation (Thr-Ala877), resulting in a partial loss of AR's ligand specificity. We speculate that the AR in LNCaP mediated not only DHT-, but also E2- and R5020-induced gene regulations. On the other hand, there have been no reports indicating such a mutation leads to interaction between AR and either vitamin D3 or dexamethasone in these cells. Collectively, we raise a possibility that a mutated or non-mutated AR could elicit ligand-induced gene expression through a complex network of nuclear interwoven signaling cascades.
Nothing to Disclose: TS, TK, MI, MT, TO
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