Objective: Endometrial cells may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of DJ-1 and phosphorylated mammalian target of rapamycin (p-mTOR) in ectopic and eutopic endometria of endometriosis and adenomyosis. Methods: Endometrial specimens were obtained from healthy non-menopausal women (n = 17) or patients with ovarian endometriotic cysts (n = 48) or adenomyosis (n = 30) during January 2011 to June 2012. The expressions of DJ-1 and p-mTOR were evaluated by immunohistochemistry and western blotting methods. Results: The expressions of DJ-1 and p-mTOR were significantly higher in the ectopic endometria than those in the eutopic endometria of endometriosis and adenomyosis patients or normal endometria (FDR < 0.05). DJ-1 expression was positively correlated with the p-mTOR expression no matter at endometriosis (r = 0.736, FDR < 0.001) or adenomyosis (r = 0.809, FDR < 0.001). Conclusion: DJ-1 protein may be involved in endometrial cells proliferation, migration and angiogenesis by modulating the PI3K/Akt/p-mTOR signaling pathway, which provides an underlying theoretical target for endometriosis and adenomyosis.

Keywords:
Endometriosis, Adenomyosis, DJ-1, p-mTOR
1.
Varma R, Soneja H, Samuel N, Sangha E, Clark TJ, Gupta JK: Outpatient Thermachoice endometrial balloon ablation: long-term, prognostic and quality-of-life measures. Gynecol Obstet Invest 2010;70:145-148.
2.
Ulker V, Tunca A, Numanoglu C, Akbayir O, Akyol A, Erim A, et al: Should omentectomy be a part of surgical staging in patients with endometrioid adenocarcinoma of the uterine corpus. Gynecol Obstet Invest 2014;77:58-63.
3.
Sampson JA: Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422-469.
4.
Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughan SL, Centonze VE, Schenken RS: Pathogenesis of endometriosis - current research. Hum Fertil (Camb) 2003;6:34-40.
5.
Matsuzaki S, Maleysson E, Darcha C: Analysis of matrix metalloproteinase-7 expression in eutopic and ectopic endometrium samples from patients with different forms of endometriosis. Hum Reprod 2010;25:742-750.
6.
Xu YL, Wang DB, Liu QF, Chen YH, Yang Z: Silencing of cofilin-1 gene attenuates biological behaviours of stromal cells derived from eutopic endometria of women with endometriosis. Hum Reprod 2010;25:2480-2488.
7.
dos Santos Hidalgo G, Meola J, Rosa e Silva JC, Paro de Paz CC, Ferriani RA: TAGLN expression is deregulated in endometriosis and may be involved in cell invasion, migration, and differentiation. Fertil Steril 2011;96:700-703.
8.
Locci R, Nisolle M, Angioni S, Foidart JM, Munaut C: Expression of the gamma 2 chain of laminin-332 in eutopic and ectopic endometrium of patients with endometriosis. Reprod Biol Endocrinol 2013;11:94.
9.
Rai P, Kota V, Deendayal M, Shivaji S: Differential proteome profiling of eutopic endometrium from women with endometriosis to understand etiology of endometriosis. J Proteome Res 2010;9:4407-4419.
10.
Rai P, Shivaji S: The role of DJ-1 in the pathogenesis of endometriosis. PLoS One 2011;6:e18074.
11.
Zoncu R, Efeyan A, Sabatini DM: mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12:21-35.
12.
Slomovitz BM, Coleman RL: The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res 2012;18:5856-5864.
13.
Torres A, Torres K, Pesci A, Ceccaroni M, Paszkowski T, Cassandrini P, et al: Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma. BMC Cancer 2012;12:369.
14.
Mettler L, Salmassi A, Schollmeyer T, Schmutzler AG, Püngel F, Jonat W: Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis). J Assist Reprod Genet 2007;24:249-258.
15.
Borghese B, Mondon F, Noël JC, Fayt I, Mignot TM, Vaiman D, et al: Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenic potential. Mol Endocrinol 2008;22:2557-2562.
16.
Benagiano G, Brosens I, Habiba M: Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update 2014;20:386-402.
17.
Leyendecker G, Wildt L, Mall G: The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 2009;280:529-538.
18.
Revised american society for reproductive medicine classification of endometriosis: 1996. Fertil Steril 1997;67:817-821.
19.
Sun L, Wang J, Zhang L, Li X, Shen D: Expression of ER-α36, a novel variant of estrogen receptor in endometrial carcinoma and its clinical significance. Gynecol Obstet Invest 2013;75:68-72.
20.
Kao AP, Wang KH, Chang CC, Lee JN, Long CY, Chen HS, et al: Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model. Fertil Steril 2011;95:1308-1315.e1.
21.
Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, et al: Oestrogen-induced epithelial--mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol 2010;222:261-270.
22.
Kitawaki J: Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 2006;20:493-502.
23.
Varma R, Rollason T, Gupta JK, Maher ER: Endometriosis and the neoplastic process. Reproduction 2004;127:293-304.
24.
Leconte M, Nicco C, Ngô C, Chéreau C, Chouzenoux S, Marut W, et al: The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice. Am J Pathol 2011;179:880-889.
25.
Becker CM, Rohwer N, Funakoshi T, Cramer T, Bernhardt W, Birsner A, et al: 2-Methoxyestradiol inhibits hypoxia-inducible factor-1α and suppresses growth of lesions in a mouse model of endometriosis. Am J Pathol 2008;172:534-544.
26.
Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T: Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2005;11:63-70.
27.
Wu MH, Lu CW, Chang FM, Tsai SJ: Estrogen receptor expression affected by hypoxia inducible factor-1α in stromal cells from patients with endometriosis. Taiwan J Obstet Gynecol 2012;51:50-54.
28.
Vasseur S, Afzal S, Tardivel-Lacombe J, Park DS, Iovanna JL, Mak TW: DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci U S A 2009;106:1111-1116.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.