Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation

被引：81

作者：

Bianco, Stephanie ^{[1
]}

Lanvin, Olivia ^{[1
]}

Tribollet, Violaine ^{[1
]}

Macari, Claire ^{[1
]}

North, Sophie ^{[2
,3
]}

Vanacker, Jean-Marc ^{[1
]}

机构：

[1] Univ Lyon 1, Inst Genom Fonct Lyon, INRA, Ecole Normale Super Lyon,CNRS, F-69364 Lyon 07, France

[2] Univ Bordeaux 1, F-33400 Talence, France

[3] INSERM, U920, F-33400 Talence, France

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 35期

关键词：

BREAST-CANCER CELLS; INDEPENDENT TRANSCRIPTIONAL ACTIVATION; ERR-ALPHA; THERAPEUTIC TARGET; GENE-TRANSCRIPTION; NUCLEAR RECEPTORS; PROSTATE-CANCER; ORPHAN RECEPTOR; SP1; SITES; EXPRESSION;

D O I：

10.1074/jbc.M109.028191

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 ERR alpha reduces the proliferation of various cell lines and blocks the G(1)/S transition of the cell cycle in an ERR alpha-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21(waf/cip1) at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice.

引用

页码：23286 / 23292

页数：7

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