Estrogen receptor β regulates endometriotic cell survival through serum and glucocorticoid-regulated kinase activation

雌激素受体 β 通过血清和糖皮质激素调节激酶激活来调节子宫内膜异位细胞存活

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作者:Diana Monsivais, Matthew T Dyson, Ping Yin, Antonia Navarro, John S Coon Th, Mary Ellen Pavone, Serdar E Bulun

Objective

To determine the expression and biological roles of serum and glucocorticoid-regulated kinase (SGK1) in tissues and cells from patients with endometriosis and from healthy control subjects. Design: Case-control. Setting: University research setting. Patient(s): Premenopausal women. Intervention(s): Endometriotic tissues were obtained from women with ovarian endometriosis, and normal endometrial tissues were obtained from women undergoing hysterectomy for benign conditions. Main outcome measure(s): Expression levels of SGK1, the role of SGK1 in endometriosis pathology, and regulation of SGK1 by estrogen receptor (ER) β. Result(s): Transcript and protein levels of SGK1 were significantly higher in endometriotic tissues and cells compared with normal endometrium. SGK1 mRNA and protein levels were stimulated by E2, by the ERβ-selective agonist diarylpropionitrile, and by prostaglandin E2. SGK1 was transcriptionally regulated by ERβ based on small interfering RNA knockdown and chromatin immunoprecipitation of ERβ followed by quantitative polymerase chain reaction. SGK1 knockdown led to increased cleavage of poly(ADP-ribose) polymerase, and SGK1 activation was correlated with the phosphorylation of FOXO3a, a proapoptotic factor.

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