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Archives of Gynecology and Obstetrics

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01.01.2016 | General Gynecology

The co-expression of GPER and Gankyrin in ovarian endometriosis and its correlation with the rASRM stages

verfasst von: Chun Zhang, Xiying Yuan, Yi Zhang

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 1/2016

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Abstract

Objective

The aim of this study was to examine the expression of G protein-coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis, analyze their clinicopathological significance, and investigate their correlation.

Methods

Quantitative real-time polymerase chain reaction and Western blot were performed to testify mRNA and protein expression of GPER and Gankyrin in ovarian endometriosis. Immunohistochemical staining (streptavidin–peroxidase method) was conducted to determine the expression and distribution of GPER and Gankyrin protein in matched ectopic and eutopic endometrium of endometriosis and normal endometrium. We also investigated their associations with rASRM stages and the correlation between the two proteins.

Results

GPER and Gankyrin were found overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients. The immunohistochemical analysis also revealed that higher expression was observed in eutopic endometrium with or without endometriosis during proliferative phase in comparison to secretory phase. These two proteins were positively correlated with the stages of endometriosis. Moreover, a significant positive correlation was found between GPER and Gankyrin both in ectopic and eutopic endometrium of the ovarian endometriosis.

Conclusion

GPER and Gankyrin might be implicated in the hormonal regulation of endometriosis and be associated with the severity of endometriosis. In addition, GPER and Gankyrin were found to be positively correlated, which could possibly serve as novel therapeutic targets for this disease.

Vercellini P, Viganò P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10(5):261–275PubMedCrossRef

Shao R, Cao S, Wang X, Feng Y, Billiq H (2014) The elusive and controversial roles of estrogen and progesterone receptors in human endometriosis. Am J Transl Res 6(2):104–113PubMedPubMedCentral

Du GQ, Zhou L, Chen XY, Wan XP, He YY (2012) The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells. Biochem Biophys Res Commun 420(2):343–349PubMedCrossRef

Lin BC, Suzawa M, Blind RD, Tobias SC, Bulun SE, Scanlan TS et al (2009) Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res 69(13):5415–5423PubMedPubMedCentralCrossRef

Prossnitz ER, Barton M (2011) The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 7(12):715–726PubMedPubMedCentralCrossRef

Filardo EJ, Quinn JA, Sabo E (2008) Association of the membrane estrogen receptor, GPR30, with breast tumor metastasis and transactivation of the epidermal growth factor receptor. Steroids 73(9–10):870–873PubMedCrossRef

He YY, Cai B, Yang YX, Liu XL, Wan XP (2009) Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci 100(6):1051–1061PubMedCrossRef

Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE et al (2007) GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol 196(4):386.e1–386.e9 (discussion 386.e9–11) CrossRef

Heublein S, Lenhard M, Vrekoussis T, Schoepfer J, Kuhn C, Friese K et al (2012) The G-protein-coupled estrogen receptor (GPER) is expressed in normal human ovaries and is upregulated in ovarian endometriosis and pelvic inflammatory disease involving the ovary. Reprod Sci 19(11):1197–1204PubMedCrossRef

10.

Heublein S, Vrekoussis T, Kuhn C, Friese K, Makrigiannakis A, Mayr D et al (2013) Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis: potential implications for macrophages and follicle maturation. J Reprod Immunol 97(1):95–103PubMedCrossRef

11.

Yuguchi H, Tanabe A, Hayashi A, Tanaka Y, Okuda K, Yamashita Y et al (2013) The expression status of G protein-coupled receptor GPR30 is associated with the clinical characteristics of endometriosis. Endocr Res 38(4):223–231PubMedCrossRef

12.

Kim YH, Kim JH, Choi YW, Lim SK, Yim H, Kang SY et al (2013) Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression. Exp Mol Pathol 94(2):360–365PubMedCrossRef

13.

Zhang J, Yang Y, Zhang Z, He Y, Liu Z, Yu Y et al (2013) Gankyrin plays an essential role in estrogen-driven and GPR30-mediated endometrial carcinoma cell proliferation via the PTEN/PI3K/AKT signaling pathway. Cancer Lett 339(2):279–287PubMedCrossRef

14.

Fu J, Chen Y, Cao J, Luo T, Qian YW, Yang W et al (2011) p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1alpha pathways. Hepatology 53(1):181–192PubMedCrossRef

15.

Lozano G, Zambetti GP (2005) Gankyrin: an intriguing name for a novel regulator of p53 and RB. Cancer Cell 8(1):3–4PubMedCrossRef

16.

(1997) Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 67(5):817–821

17.

Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT et al (1986) Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 46(10):5419–5425PubMed

18.

Rizner TL (2009) Estrogen metabolism and action in endometriosis. Mol Cell Endocrinol 307(1–2):8–18PubMedCrossRef

19.

Samartzis N, Samartzis EP, Noske A, Fedier A, Dedes KJ, Caduff R et al (2012) Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study. Reprod Biol Endocrinol 10:30PubMedPubMedCentralCrossRef

20.

Liu H and Lang JH (2011) Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis. Med Sci Monit 17(4):RA92–RA99

21.

Thomas P, Pang Y, Filardo EJ, Dong J (2005) Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology 146(2):624–632PubMedCrossRef

22.

Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307(5715):1625–1630PubMedCrossRef

23.

Pupo M, Vivacqua A, Perrotta I, Pisano A, Aquila S, Abonante S et al (2013) The nuclear localization signal is required for nuclear GPER translocation and function in breast Cancer-Associated Fibroblasts (CAFs). Mol Cell Endocrinol 376(1–2):23–32PubMedCrossRef

24.

Goncalves GA, Camargo-Kosugi CM, Bonetti TC, Invitti AL, Girão MJ, Silva ID et al (2015) p27 (kip1) overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis. Apoptosis 20(3):327–335PubMedCrossRef

25.

Dong LW, Yang GZ, Pan YF, Chen Y, Tan YX, Dai RY et al (2011) The oncoprotein p28GANK establishes a positive feedback loop in beta-catenin signaling. Cell Res 21(8):1248–1261PubMedPubMedCentralCrossRef

26.

Matsuzaki S, Darcha C (2012) Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod 27(3):712–721PubMedCrossRef

27.

Bartley J, Jülicher A, Hotz B, Mechsner S, Hotz H (2014) Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium. Arch Gynecol Obstet 289(4):871–881PubMedCrossRef

28.

Plante BJ, Lessey BA, Taylor RN, Wang W, Bagchi MK, Yuan L et al (2012) G protein-coupled estrogen receptor (GPER) expression in normal and abnormal endometrium. Reprod Sci 19(7):684–693PubMedPubMedCentralCrossRef

29.

Iwai A, Marusawa H, Kiuchi T, Higashitsuji H, Tanaka K, Fujita J et al (2003) Role of a novel oncogenic protein, gankyrin, in hepatocyte proliferation. J Gastroenterol 38(8):751–758PubMedCrossRef

Titel: The co-expression of GPER and Gankyrin in ovarian endometriosis and its correlation with the rASRM stages
verfasst von: Chun Zhang
Xiying Yuan
Yi Zhang
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 1/2016
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-015-3807-x

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The co-expression of GPER and Gankyrin in ovarian endometriosis and its correlation with the rASRM stages

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