Modulating estrogen receptor-related receptor-alpha activity inhibits cell proliferation.
High expression of the estrogen receptor-related receptor (ERR)-alpha in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRalpha reduces the proliferation of various cell lines and blocks the G(1)/S transition of the cell cycle in an ERRalpha-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21(waf/cip)(1) at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice.
Bianco
Stéphanie
S
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, France.
Lanvin
Olivia
O
Tribollet
Violaine
V
Macari
Claire
C
North
Sophie
S
Vanacker
Jean-Marc
JM
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009570:Nitriles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor
D009570:Nitriles; D011960:Receptors, Estrogen; D013844:Thiazoles; D000097983:ERRalpha Estrogen-Related Receptor; C488234:XCT790