Abstract
Endometriosis is an estrogen-dependent disease, causing pelvic pain and infertility. c-fos is an early transcription factor that has been reported to be related to estradiol-dependent cell proliferation. The aim of the present study was to assess the c-fos gene and protein expression in pelvic endometriotic implants in comparison to normal endometrium from infertile women. An open, prospective and controlled study included 15 infertile women with endometriosis and 19 control infertile women. Endometrial and endometriotic biopsies were performed at the follicular phase and the samples were processed for RT-PCR and immunohistochemistry. ERα mRNA levels were similar in the endometriotic implants/eutopic endometrium from women with endometriosis and in normal tissue (P = 0.649). The aromatase gene, however, was not expressed in the eutopic endometrium from either control or endometriosis groups, and was only expressed in 50% of endometriotic implants (P = 0.044). c-fos gene expression was higher in endometriotic implants (1.32 ± 0.13; P = 0.011) than in eutopic endometrium from patients with endometriosis (0.97 ± 0.11) or from the control group (0.91 ± 0.05). In addition, immunohistochemistry showed a more abundant distribution of c-Fos in the stroma of endometriotic tissue compared to eutopic endometrium. These data suggest that c-fos may play a role in the molecular mechanisms of estrogen action on the induction, promotion or progression of endometriosis.
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References
Asschert JG, De Vries EG, De Jong S, Withoff S, Vellenga E (1999) Differential regulation of IL-6 promoter activity in a human ovarian-tumor cell line transfected with various p53 mutants: involvement of AP-1. Int J Cancer 81:236–242. doi:10.1002/(SICI)1097-0215(19990412)81:2;3.0.CO;2-R
Crowe DL, Brown TN, Kim R, Smith SM, Lee MK (2000) A c-fos/estrogen receptor fusion protein promotes cell cycle progression and proliferation of human cancer cell lines. Mol Cell Biol Res Commun 3:243–248. doi:10.1006/mcbr.2000.0221
Dotzlaw H, Leygue E, Watson PH, Murphy LC (1997) Expression of estrogen receptor-beta in human breast tumors. J Clin Endocrinol Metab 82:2371–2374. doi:10.1210/jc.82.7.2371
Eskenazi B, Warner ML (1997) Epidemiology of endometriosis. Obstet Gyn Clin N Am 24:235–258. doi:10.1016/S0889-8545(05)70302-8
Fujishita A, Nakane PK, Koji T, Masuzaki H, Chavez RO, Yamabe T et al (1997) Expression of estrogen and progesterone receptors in endometrium and peritoneal endometriosis: an immunohistochemical and in situ hybridization study. Fertil Steril 67:856–864. doi:10.1016/S0015-0282(97)81397-0
Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799. doi:10.1016/S0140-6736(04)17403-5
Gussow D, Rein R, Ginjaar I, Hochstenbach F, Seemann G, Kottman A et al (1987) The human beta 2-microglobulin gene. Primary structure and definition of the transcriptional unit. J Immunol 139:3132–3138
Hennessy BA, Harvey BJ, Healy V (2005) 17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells. Mol Cell Endocrinol 229:39–47. doi:10.1016/j.mce.2004.10.001
Huang J, Shi YF, Zhou CY (2005) Expressions of aromatase P450 and estrogen receptor in eutopic and ectopic endometrium in endometriosis and their correlation with endometriosis. Zhonghua Fu Chan Ke Za Zhi 40:171–174
Lee YN, Tuckerman J, Nechushtan H, Schutz G, Razin E, Angel P (2004) c-Fos as a Regulator of Degranulation and Cytokine Production in Fc_RI-Activated Mast Cells. J Immunol 173:2571–2577
Luo X, Ding L, Chegini N (2004) Gonadotropin-releasing hormone and TGF-beta activate MAP kinase and differentially regulate fibronectin expression in endometrial epithelial and stromal cells. Am J Physiol Endocrinol Metab 287:E991–E1001. doi:10.1152/ajpendo.00200.2004
Matsuzaki S, Uehara S, Murakami T, Fujiwara J, Funato T, Okamura K (2000) Quantitative analysis of estrogen receptor alpha and beta messenger ribonucleic acid levels in normal endometrium and ovarian endometriotic cysts using a real-time reverse transcription-polymerase chain reaction assay. Fertil Steril 74:753–759. doi:10.1016/S0015-0282(00)00712-3
Matsuzaki S, Murakami T, Uehara S, Canis M, Sasano H, Okamura K (2001) Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis. Fertil Steril 75:1198–1205. doi:10.1016/S0015-0282(01)01783-6
McClelland RA, Finlay P, Walker KJ, Nicholson D, Robertson JF, Blamey RW, Nicholson RI (1990) Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer. Cancer Res 50:3545–3550
Noble LS, Simpson ER, Johns A, Bulun SE (1996) Aromatase expression in endometriosis. J Clin Endocrinol Metab 81:174–179. doi:10.1210/jc.81.1.174
Oliveira IO, Lhullier C, Brum IS, Spritzer PM (2003) Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women. Steroids 68:641–649. doi:10.1016/S0039-128X(03)00093-X
Othman EE, Salama S, Ismail N, Al-Hendy A (2007) Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells. Fertil Steril 88:462–471. doi:10.1016/j.fertnstert.2006.11.046
Pan H, Sheng JZ, Tang L, Zhu R, Zhou TH, Huang HF (2008) Increased expression of c-fos protein associated with increased matrix metalloproteinase-9 protein expression in the endometrium of endometriotic patients. Fertil Steril 90:1000–1007. doi:10.1016/j.fertnstert.2007.07.1386
Reis FM, Maia AL, Ribeiro MF, Spritzer PM (1999) Progestin modulation of c-fos and prolactin gene expression in the human endometrium. Fertil Steril 71:1125–1132. doi:10.1016/S0015-0282(99)00138-7
Rossi D, Del Giacco L, Doneda L, Nicolini U, Acaia B, Brioschi D (1996) Expression pattern of c-sis, c-fos and c-jun in human placenta and embryofetal organs. Gynecol Obstet Invest 42:1–7
Sampson JA (1927) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–425
Shaulian E, Karin M (2001) AP-1 in cell proliferation and survival. Oncogene 20:2390–2400. doi:10.1038/sj.onc.1204383
The American Society for Reproductive Medicine (1997) Revised American Society for Reproductive Medicine classification of endometriosis. Fertil Steril 67:817–821. doi:10.1016/S0015-0282(97)81391-X
Weisz A, Rosales R (1990) Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor. Nucleic Acids Res 18:5097–5106. doi:10.1093/nar/18.17.5097
Yang WC, Chen HW, Au HK, Chang CW, Huang CT, Yen YH et al (2004) Endometriosis. Serum and endometrial markers. Best Pract Res Clin Obstet Gynaecol 18:305–318. doi:10.1016/j.bpobgyn.2004.03.003
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This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa de Apoio aos Núcleos de Excelência em Pesquisa (PRONEX).
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Morsch, D.M., Carneiro, M.M., Lecke, S.B. et al. c-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action. J Mol Hist 40, 53–58 (2009). https://doi.org/10.1007/s10735-009-9212-7
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DOI: https://doi.org/10.1007/s10735-009-9212-7