{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:28:51Z","timestamp":1790882931808,"version":"4.1.0"},"reference-count":57,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The function of estrogen receptor beta (ER-\u03b2) in mammary tissue is not completely understood. While early observations were often conflicting, more recent data suggest an important role as a tumor-suppressor gene. A decrease of ER-\u03b2 expression has been observed in ductal carcinoma in situ and invasive carcinoma as compared with benign mammary epithelial cells. The loss of ER-\u03b2 resulted in abnormal growth of mammary epithelial cells. We have previously shown that the mRNA expression of the ER-\u03b2 gene is almost totally suppressed in breast carcinomas from patients with a poor prognosis. Here we analyzed whether methylation changes in the different promoters of ER-\u03b2 are responsible for the loss of expression of the gene. A methylation assay with high specificity and sensitivity was developed, and a panel of breast tissue samples (n = 175) was characterized for methylation status. In contrast to benign breast, more than two-thirds of invasive breast cancers showed a high degree of methylation. Importantly, increased methylation was also detectable in numerous premalignant lesions. By analysis of breast tumors, previously characterized by gene-expression profiling, methylation was predominantly detected in a subgroup of patients with an unfavorable prognosis, suggesting a possible prognostic value of the ER-\u03b2 methylation status. We also investigated the structural characteristics of the two ER-\u03b2 promoters, which were both found to be closely associated with a second, downstream, localized and opposite-oriented promoter. However, we could not detect endogenous antisense RNA transcribed from these promoters, which may be involved in epigenetic gene silencing. We also failed to induce ER-\u03b2 promoter methylation by expressing siRNAs in cell lines. Interestingly, by comparing the promoter sequences of ER-\u03b2 with other genes known to be epigenetically inactivated in breast cancers, we identified a sequence motif possibly involved in promoter methylation.<\/jats:p>","DOI":"10.1677\/erc.1.01088","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T14:06:49Z","timestamp":1133446009000},"page":"903-916","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":69,"title":["Methylation of estrogen receptor \u03b2 promoter correlates with loss of ER-\u03b2 expression in mammary carcinoma and is an early indication marker in premalignant lesions"],"prefix":"10.1530","volume":"12","author":[{"given":"A","family":"Rody","sequence":"first","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Holtrich","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Solbach","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Kourtis","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"von Minckwitz","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"2German Breast Group, Schleussnerstrasse 42, 63263 Neu-Isenburg\/Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Engels","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kissler","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Ga\u0308tje","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Karn","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"1Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070909185313600_AHR-ETAL-2001","doi-asserted-by":"crossref","unstructured":"Ahr\n              A\n            \n          , Holtrich U, Solbach C, Scharl A, Strebhardt K, Karn T & Kaufmann M 2001 Molecular classification of breast cancer patients by gene expression profiling. 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