The orphan receptor ERRalpha interferes with steroid signaling.
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.
Teyssier
Catherine
C
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, INRA, 69364 Lyon cedex 07, France.
Bianco
Stéphanie
S
Lanvin
Olivia
O
Vanacker
Jean-Marc
JM
D000728:Androgens / Q000502:physiology*; D045744:Cell Line, Tumor; D054314:Drug Inverse Agonism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020218:Response Elements; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D015533:Transcriptional Activation; D000097983:ERRalpha Estrogen-Related Receptor
D000728:Androgens; D009570:Nitriles; D017430:Prostate-Specific Antigen; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013844:Thiazoles; D000097983:ERRalpha Estrogen-Related Receptor; C488234:XCT790