xct790 and Prostatic-Neoplasms

The estrogen receptor-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily that has been shown to interfere with the estrogen-signaling pathway. In this report, we demonstrate that ERRalpha also cross-talks with signaling driven by other steroid hormones. Treatment of human prostatic cells with a specific ERRalpha inverse agonist reduces the expression of several androgen-responsive genes, in a manner that does not involve perturbation of androgen receptor expression or activity. Furthermore, ERRalpha activates the expression of androgen response elements (ARE)-containing promoters, such as that of the prostate cancer marker PSA, in an ARE-dependent manner. In addition, promoters containing a steroid response element can be activated by all members of the ERR orphan receptor subfamily, and this, even in the presence of antisteroid compounds.

Topics: Androgens; Cell Line, Tumor; Drug Inverse Agonism; ERRalpha Estrogen-Related Receptor; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Response Elements; Signal Transduction; Thiazoles; Transcriptional Activation