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Erschienen in: Archives of Gynecology and Obstetrics 2/2017

03.06.2017 | General Gynecology

Promotor analysis of ESR1 in endometrial cancer cell lines, endometrial and endometriotic tissue

verfasst von: Vanessa Toderow, Martina Rahmeh, Simone Hofmann, Verena Kirn, Sven Mahner, Udo Jeschke, Viktoria von Schönfeldt

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 2/2017

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Abstract

Purpose

The nuclear hormone receptor estrogen receptor α (ERα) is pivotal for numerous processes in the cell. As a transcription factor, it regulates eukaryotic gene expression and affects cellular proliferation and differentiation in target tissues. Moreover, ERα is known for its influence on various gynecological diseases and carcinogenesis. Since its expression is often altered in diseased tissues and this alteration was found to be caused by hypermethylation of the ESR1 promotor region in cancer, including breast and colorectal cancer, the aim of this study is to elucidate if the expression of ERα is also regulated epigenetically in endometriosis and endometrial cancer.

Methods

Using real-time methylation-specific PCR (rt-MSP), we examined endometrial and endometriotic tissues as well as five endometrial cancer cell lines and compared the methylation status with the actual expression of ERα.

Results

The results of our study indicate that, though its expression is altered in endometrial and endometriotic tissue, ERα is not regulated by methylation of the promotor region in endometriosis. In contrast, three of the five endometrial cancer cell lines are methylated in the promotor region of ESR1.

Conclusions

Thus, further investigation of the connection between ERα and endometrial cancer will be the next step.
Literatur
1.
Zurück zum Zitat Ali SH, O’donnell AL, Mohamed S et al (2004) Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors. Gynecol Oncol 95:637–645CrossRefPubMed Ali SH, O’donnell AL, Mohamed S et al (2004) Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors. Gynecol Oncol 95:637–645CrossRefPubMed
2.
Zurück zum Zitat Berger U, Mcclelland RA, Wilson P et al (1991) Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis. Can Res 51:239–244 Berger U, Mcclelland RA, Wilson P et al (1991) Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis. Can Res 51:239–244
3.
Zurück zum Zitat Bloski T, Pierson R (2008) Endometriosis and chronic pelvic pain: unraveling the mystery behind this complex condition. Nurs Women’s Health 12:382–395CrossRef Bloski T, Pierson R (2008) Endometriosis and chronic pelvic pain: unraveling the mystery behind this complex condition. Nurs Women’s Health 12:382–395CrossRef
4.
Zurück zum Zitat Bopp B, Shoupe D (1993) Luteal phase defects. J Reprod Med 38:348–356PubMed Bopp B, Shoupe D (1993) Luteal phase defects. J Reprod Med 38:348–356PubMed
5.
Zurück zum Zitat Cunha-Filho JS, Gross JL, Bastos De Souza CA et al (2003) Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet 20:117–121CrossRefPubMedPubMedCentral Cunha-Filho JS, Gross JL, Bastos De Souza CA et al (2003) Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet 20:117–121CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Eads CA, Lord RV, Kurumboor SK et al (2000) Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Can Res 60:5021–5026 Eads CA, Lord RV, Kurumboor SK et al (2000) Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Can Res 60:5021–5026
7.
Zurück zum Zitat Eeckhoute J, Keeton EK, Lupien M et al (2007) Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Can Res 67:6477–6483CrossRef Eeckhoute J, Keeton EK, Lupien M et al (2007) Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Can Res 67:6477–6483CrossRef
8.
Zurück zum Zitat Elledge RM, Green S, Pugh R et al (2000) Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer 89:111–117CrossRefPubMed Elledge RM, Green S, Pugh R et al (2000) Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer 89:111–117CrossRefPubMed
9.
Zurück zum Zitat Engemise SL, Willets JM, Taylor AH et al (2011) Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol 157:101–106CrossRefPubMed Engemise SL, Willets JM, Taylor AH et al (2011) Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol 157:101–106CrossRefPubMed
10.
Zurück zum Zitat Esteller M, Corn PG, Baylin SB et al (2001) A gene hypermethylation profile of human cancer. Can Res 61:3225–3229 Esteller M, Corn PG, Baylin SB et al (2001) A gene hypermethylation profile of human cancer. Can Res 61:3225–3229
11.
Zurück zum Zitat Harder J, Engelstaedter V, Usadel H et al (2009) CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 100:360–365CrossRefPubMedPubMedCentral Harder J, Engelstaedter V, Usadel H et al (2009) CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 100:360–365CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Holmes KA, Song JS, Liu XS et al (2008) Nk3–1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity. Can Res 68:7380–7385CrossRef Holmes KA, Song JS, Liu XS et al (2008) Nk3–1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity. Can Res 68:7380–7385CrossRef
13.
Zurück zum Zitat Holst F, Hoivik EA, Gibson WJ et al (2016) Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth. Sci Rep 6:25521CrossRefPubMedPubMedCentral Holst F, Hoivik EA, Gibson WJ et al (2016) Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth. Sci Rep 6:25521CrossRefPubMedPubMedCentral
14.
15.
Zurück zum Zitat Hurtado A, Holmes KA, Geistlinger TR et al (2008) Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 456:663–666CrossRefPubMedPubMedCentral Hurtado A, Holmes KA, Geistlinger TR et al (2008) Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 456:663–666CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Issa JP, Ottaviano YL, Celano P et al (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540CrossRefPubMed Issa JP, Ottaviano YL, Celano P et al (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540CrossRefPubMed
17.
Zurück zum Zitat Issa JP, Zehnbauer BA, Civin CI et al (1996) The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Can Res 56:973–977 Issa JP, Zehnbauer BA, Civin CI et al (1996) The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Can Res 56:973–977
18.
Zurück zum Zitat Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed
19.
Zurück zum Zitat Jongen V, Briet J, De Jong R et al (2009) Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 112:537–542CrossRefPubMed Jongen V, Briet J, De Jong R et al (2009) Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 112:537–542CrossRefPubMed
20.
22.
Zurück zum Zitat Lapidus RG, Ferguson AT, Ottaviano YL et al (1996) Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res Off J Am Assoc Cancer Res 2:805–810 Lapidus RG, Ferguson AT, Ottaviano YL et al (1996) Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res Off J Am Assoc Cancer Res 2:805–810
23.
Zurück zum Zitat Lapidus RG, Nass SJ, Butash KA et al (1998) Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Can Res 58:2515–2519 Lapidus RG, Nass SJ, Butash KA et al (1998) Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Can Res 58:2515–2519
24.
Zurück zum Zitat Lapidus RG, Nass SJ, Davidson NE (1998) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mamm Gland Biol Neoplasia 3:85–94CrossRef Lapidus RG, Nass SJ, Davidson NE (1998) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mamm Gland Biol Neoplasia 3:85–94CrossRef
25.
26.
Zurück zum Zitat Liu X, Shi H (2015) Regulation of estrogen receptor α expression in the hypothalamus by sex steroids: implication in the regulation of energy homeostasis. Int J Endocrinol 2015:949085PubMedPubMedCentral Liu X, Shi H (2015) Regulation of estrogen receptor α expression in the hypothalamus by sex steroids: implication in the regulation of energy homeostasis. Int J Endocrinol 2015:949085PubMedPubMedCentral
27.
Zurück zum Zitat Matorras R, Rodriguez F, Perez C et al (1996) Infertile women with and without endometriosis: a case control study of luteal phase and other infertility conditions. Acta Obstet Gynecol Scand 75:826–831CrossRefPubMed Matorras R, Rodriguez F, Perez C et al (1996) Infertile women with and without endometriosis: a case control study of luteal phase and other infertility conditions. Acta Obstet Gynecol Scand 75:826–831CrossRefPubMed
28.
Zurück zum Zitat Moeloek FA, Moegny E (1993) Endometriosis and luteal phase defect. Asia Ocean J Obstetr Gynaecol 19:171–176CrossRef Moeloek FA, Moegny E (1993) Endometriosis and luteal phase defect. Asia Ocean J Obstetr Gynaecol 19:171–176CrossRef
29.
Zurück zum Zitat Pandya KJ, Yeap BY, Weiner LM et al (2001) Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol 24:43–46CrossRefPubMed Pandya KJ, Yeap BY, Weiner LM et al (2001) Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol 24:43–46CrossRefPubMed
30.
Zurück zum Zitat Rendina GM, Donadio C, Fabri M et al (1984) Tamoxifen and medroxyprogesterone therapy for advanced endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol 17:285–291CrossRefPubMed Rendina GM, Donadio C, Fabri M et al (1984) Tamoxifen and medroxyprogesterone therapy for advanced endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol 17:285–291CrossRefPubMed
31.
Zurück zum Zitat Rogers PA, D’hooghe TM, Fazleabas A et al (2009) Priorities for endometriosis research: recommendations from an international consensus workshop. Reprod Sci (Thousand Oaks, Calif) 16:335–346CrossRef Rogers PA, D’hooghe TM, Fazleabas A et al (2009) Priorities for endometriosis research: recommendations from an international consensus workshop. Reprod Sci (Thousand Oaks, Calif) 16:335–346CrossRef
32.
Zurück zum Zitat Ross-Innes CS, Stark R, Holmes KA et al (2010) Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev 24:171–182CrossRefPubMedPubMedCentral Ross-Innes CS, Stark R, Holmes KA et al (2010) Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev 24:171–182CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Thigpen T, Brady MF, Homesley HD et al (2001) Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 19:364–367CrossRefPubMed Thigpen T, Brady MF, Homesley HD et al (2001) Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 19:364–367CrossRefPubMed
34.
Zurück zum Zitat Yue W, Yager JD, Wang JP et al (2013) Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78:161–170CrossRefPubMed Yue W, Yager JD, Wang JP et al (2013) Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78:161–170CrossRefPubMed
Metadaten
Titel
Promotor analysis of ESR1 in endometrial cancer cell lines, endometrial and endometriotic tissue
verfasst von
Vanessa Toderow
Martina Rahmeh
Simone Hofmann
Verena Kirn
Sven Mahner
Udo Jeschke
Viktoria von Schönfeldt
Publikationsdatum
03.06.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 2/2017
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-017-4405-x

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