{"paper_id":"4d45a391-fa2f-4439-ab3f-aeaeac4fe7f5","body_text":"Abstract\nConsiderable efforts have been invested in elucidating the potential mechanisms involved in the physiopathology of endometriosis. The aims of our study were to investigate whether RHOC expression is differentially altered in the endometrium and in endometriotic lesions. A total of 40 patients diagnosed with endometriosis and 15 healthy fertile women were selected for the study. Paired biopsies of endometrial tissue (eutopic endometrium) and endometriotic lesions (ectopic endometrium) were obtained from the patients with endometriosis. Endometrium from women without endometriosis was used as a control. Expression of the RHOC gene was analyzed by real-time polymerase chain reaction in autologous endometrial tissues of women with endometriosis and in the endometrium of control women. Increased RHOC expression was detected in endometriotic lesions compared to the eutopic endometrium of women with endometriosis and control women. RHOC changes may be among the key elements involved in the origin and the maintenance of endometriosis.\nSimilar content being viewed by others\nReferences\nJaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247–269.\nWheeler AP, Ridley AJ. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Exp Cell Res. 2004;301(1):43–49.\nCannizzaro LA, Madaule P, Hecht F, Axel R, Croce CM, Huebner K. Chromosome localization of human ARH genes, a ras-relate gene family. Genomics. 1990;6(2):197–203.\nHakem A, Sanchez-Sweatman O, You-Ten A, et al. RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev. 2005;19(17):1974–1979.\nMeola J, Rosa e Silva JC, Dentillo DB, et al. Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis. Fertil Steril. 2010;93(6):1750–1773.\nDentillo DB, Meola J, Rosa e Silva JC, et al. Deregulation of LOXL1 and HTRA1 Gene Expression in Endometriosis. Reprod Sci. 2010;17(11):1016–1023.\nJiang QY, Xia JM, Ding HG, Fei XW, Lin J, Wu RJ. RNAi-mediated blocking of ezrin reduces migration of ectopic endometrial cells in endometriosis. Mol Hum Reprod. 2012;18(9):435–441.\nASRM: Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.\nCook RD, Weisberg S. Transforming a response variable for linearity. Biometrika. 1994;81(4):731–737.\nVigano P, Gaffuri B, Somigliana E, Busacca M, Di Blasio AM, Vignali M. Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod. 1998;4(12):1150–1156.\nBurridge K, Wennerberg K. Rho and Rac take center stage. Cell. 2004;116(2):167–179.\nVillalonga P, Ridley AJ. Rho GTPases and cell cycle control. Growth Factors. 2006;24(3):159–164.\nPillé JY, Denoyelle C, Varet J, et al. Anti-RhoA and Anti-RhoC siRNA inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo. Mol Ther. 2005; 11(2):267–274.\nWang W, Wu F, Fang F, Tao Y, Yang L. RhoC is essential for angiogenesis induced by hepatocellular carcinoma cells via regulation of endothelial cell organization. Cancer Sci. 2008;99(10):2012–2018.\nHutchison N, Hendry BM, Sharpe CC. Rho isoforms have distinct and specific functions in the process of epithelial to mesenchymal transition in renal proximal tubular cells. Cell Signal. 2009; 21(10):1522–1531.\nWitz CA. Cell adhesion molecules and endometriosis. Semin Reprod Med. 2003;21(2):173–182.\nZhou H, Kramer RH. Integrin engagement differentially modulates epithelial cell motility by RHOA/ROCK and PAK1. J Biol Chem. 2005;280(11):10624–10635.\nWu M, Wu Z-F, Rosenthal DT, Rhee EM, Merajver SD. Characterization of the roles of RHOC and RHOA GTPases in invasion, motility and matrix adhesion in inflammatory and aggressive breast cancer. Cancer. 2010;116(suppl 11):2768–2782.\nWenandy L, Sorensen RB, Svane IM, Straten P, Andersen MH. RhoC a new target for therapeutic vaccination against metastatic cancer. Cancer Immunol Immunother. 2008; 57(12):1871–1878.\nGoodsaid FM, Smith RJ, Rosenblum IY. Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms. Environ Health Perspect. 2004; 112(4):456–460.\nPfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36.\nVan Golen KL, Bao LW, Pan Q, Miler FR, Wu ZF, Merajver SD. Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer. Clin Exp Metastasis. 2002;19(4):301–311.\nHoriuchi A, Imai T, Wang C, et al. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Lab Invest. 2003;83(6):861–870.\nSrivastava S, Ramdass B, Nagarajan S, Rehman M, Mukherjee G, Krishna S. Notch 1 regulates the functional contribution of RhoC to cervical carcinoma progression. Br J Cancer. 2010;102(1):196–205.\nWheeler AP, Ridley AJ. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Exp Cell Res. 2004;301(1):43–49.\nMcLaren J. Vascular endothelial growth factor and endometriosis. Human Reprod Update. 2000;6(1):45–55.\nMatsuzaki S, Canis M, Darcha C, Dechelotte P, Pouly JL, Bruhat MA. Fibrogenesis in peritoneal endometriosis. Gynecol Obstet Invest. 1999;47(3):197–199.\nYuge A, Nasu K, Matsumoto H, Nishida M, Narahara H. Collagen gel contractility is enhanced in human endometriotic stroml cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis. Human Reprod. 2007; 22(4):938–944.\nJiang L, Liu X, Kolokythas A, et al. Down-regulation of the Rho GTPase signaling pathway is involved in the microRNA-138 mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma. Int J Cancer. 2010;127(3):505–512.\nSahai E, Marshall CJ. Rho GTPases and câncer. Nat Rev Cancer. 2002;2(2):133–142.\nSchor E, da Silva IDCG, Sato H, Baracat EC, Girão MJBC, Freitas V. p27kip1 is down-regulated in the endometrium of women with endometriosis. Fertil Steril. 2009;91(3):682–686.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nMeola, J., Dentillo, D.B., Rosa e Silva, J.C. et al. RHOC: A Key Gene for Endometriosis. Reprod. Sci. 20, 998–1002 (2013). https://doi.org/10.1177/1933719112472743\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719112472743","source_license":"CC0","license_restricted":false}