Estrogen Receptor β Regulates Endometriotic Cell Survival Through Serum and Glucocorticoid-regulated Kinase Activation

Overview

Journal Fertil Steril

Specialty Reproductive Medicine

Date 2016 Feb 2

PMID 26827666

Citations 30

Authors

Diana Monsivais

Matthew T Dyson

Ping Yin

Antonia Navarro

John S Coon Th

Mary Ellen Pavone

Serdar E Bulun

Affiliations

Soon will be listed here.

Abstract

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.

Conclusion(s): ERβ leads to SGK1 overexpression in endometriosis, which contributes to the survival of endometriotic lesions through inhibition of apoptosis.

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References

Brunet A, Park J, Tran H, Hu L, Hemmings B, Greenberg M . Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol. 2001; 21(3):952-65. PMC: 86685. DOI: 10.1128/MCB.21.3.952-965.2001. View

Eyster K, Klinkova O, Kennedy V, Hansen K . Whole genome deoxyribonucleic acid microarray analysis of gene expression in ectopic versus eutopic endometrium. Fertil Steril. 2007; 88(6):1505-33. DOI: 10.1016/j.fertnstert.2007.01.056. View

Moragianni V . Can we finally move away from the surgical diagnosis of endometriosis?. Fertil Steril. 2012; 98(3):609. DOI: 10.1016/j.fertnstert.2012.05.028. View

Giudice L, Kao L . Endometriosis. Lancet. 2004; 364(9447):1789-99. DOI: 10.1016/S0140-6736(04)17403-5. View

Ryan I, Schriock E, Taylor R . Isolation, characterization, and comparison of human endometrial and endometriosis cells in vitro. J Clin Endocrinol Metab. 1994; 78(3):642-9. DOI: 10.1210/jcem.78.3.8126136. View

Liu Y, Gao H, Marstrand T, Strom A, Valen E, Sandelin A . The genome landscape of ERalpha- and ERbeta-binding DNA regions. Proc Natl Acad Sci U S A. 2008; 105(7):2604-9. PMC: 2268183. DOI: 10.1073/pnas.0712085105. View

Izawa M, Taniguchi F, Terakawa N, Harada T . Epigenetic aberration of gene expression in endometriosis. Front Biosci (Elite Ed). 2013; 5(3):900-10. DOI: 10.2741/e669. View

Monsivais D, Dyson M, Yin P, Coon J, Navarro A, Feng G . ERβ- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis. Mol Endocrinol. 2014; 28(8):1304-15. PMC: 4116594. DOI: 10.1210/me.2013-1421. View

Hong F, Larrea M, Doughty C, Kwiatkowski D, Squillace R, Slingerland J . mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation. Mol Cell. 2008; 30(6):701-11. DOI: 10.1016/j.molcel.2008.04.027. View

10.

Han S, Jung S, Wu S, Hawkins S, Park M, Kyo S . Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. Cell. 2015; 163(4):960-74. PMC: 4640214. DOI: 10.1016/j.cell.2015.10.034. View

11.

Charn T, Liu E, Chang E, Lee Y, Katzenellenbogen J, Katzenellenbogen B . Genome-wide dynamics of chromatin binding of estrogen receptors alpha and beta: mutual restriction and competitive site selection. Mol Endocrinol. 2009; 24(1):47-59. PMC: 2802902. DOI: 10.1210/me.2009-0252. View

12.

Feroze-Zaidi F, Fusi L, Takano M, Higham J, Salker M, Goto T . Role and regulation of the serum- and glucocorticoid-regulated kinase 1 in fertile and infertile human endometrium. Endocrinology. 2007; 148(10):5020-9. DOI: 10.1210/en.2007-0659. View

13.

Borghese B, Barbaux S, Mondon F, Santulli P, Pierre G, Vinci G . Research resource: genome-wide profiling of methylated promoters in endometriosis reveals a subtelomeric location of hypermethylation. Mol Endocrinol. 2010; 24(9):1872-85. PMC: 5417403. DOI: 10.1210/me.2010-0160. View

14.

Xue Q, Lin Z, Yin P, Milad M, Cheng Y, Confino E . Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis. J Clin Endocrinol Metab. 2007; 92(8):3261-7. DOI: 10.1210/jc.2007-0494. View

15.

Han S, Hawkins S, Begum K, Jung S, Kovanci E, Qin J . A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis. Nat Med. 2012; 18(7):1102-11. PMC: 3541027. DOI: 10.1038/nm.2826. View

16.

Simpson J, Elias S, MALINAK L, Buttram Jr V . Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol. 1980; 137(3):327-31. DOI: 10.1016/0002-9378(80)90917-5. View

17.

Nyholt D, Low S, Anderson C, Painter J, Uno S, Morris A . Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet. 2012; 44(12):1355-9. PMC: 3527416. DOI: 10.1038/ng.2445. View

18.

Zhao Y, Gong P, Chen Y, Nwachukwu J, Srinivasan S, Ko C . Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis. Sci Transl Med. 2015; 7(271):271ra9. PMC: 4790140. DOI: 10.1126/scitranslmed.3010626. View

19.

Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo S . Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005; 193(2):371-80. DOI: 10.1016/j.ajog.2005.01.034. View

20.

Keichel S, Barcena de Arellano M, Reichelt U, Riedlinger W, Schneider A, Kohler C . Lymphangiogenesis in deep infiltrating endometriosis. Hum Reprod. 2011; 26(10):2713-20. DOI: 10.1093/humrep/der230. View