ERβ- and Prostaglandin E2-Regulated Pathways Integrate Cell Proliferation via Ras-like and Estrogen-Regulated Growth Inhibitor in Endometriosis

被引：73

作者：

Monsivais, D. ^{[1
]}

Dyson, M. T. ^{[1
]}

Yin, P. ^{[1
]}

Coon, J. S. ^{[1
]}

Navarro, A. ^{[1
]}

Feng, G. ^{[2
]}

Malpani, S. S. ^{[1
]}

Ono, M. ^{[1
]}

Ercan, C. M. ^{[1
]}

Wei, J. J. ^{[3
]}

Pavone, M. E. ^{[1
]}

Su, E. ^{[1
]}

Bulun, S. E. ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol,Div Reprod Biol Res, Biomed Informat Ctr Northwestern CTSA, Chicago, IL 60611 USA

[2] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[3] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

来源：

MOLECULAR ENDOCRINOLOGY | 2014年 / 28卷 / 08期

基金：

美国国家卫生研究院;

关键词：

BREAST-CANCER; STROMAL CELLS; RECEPTOR-ALPHA; ILLUMINA MICROARRAY; MOUSE UTERUS; EXPRESSION; TRANSCRIPTION; ESTRADIOL; BINDING; GENE;

D O I：

10.1210/me.2013-1421

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-beta (ER beta) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ER beta binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ER beta target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ER beta at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ER beta and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

引用

页码：1304 / 1315

页数：12

共 52 条

[1] Estradiol and interleukin-1β exert a synergistic stimulatory effect on the expression of the chemokine regulated upon activation, normal T cell expressed, and secreted in endometriotic cells [J].