HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Rody, A Articles by Kaufmann, M Search for Related Content PubMed PubMed Citation Articles by Rody, A Articles by Kaufmann, M

¹ Department of Gynecology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
² German Breast Group, Schleussnerstrasse 42, 63263 Neu-Isenburg/Frankfurt, Germany
³ Department of Pathology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany

(Requests for offprints should be addressed to T Karn; Email: t.karn{at}em.uni-frankfurt.de)

The function of estrogen receptor beta (ER-ß) 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-ß expression has been observed in ductal carcinoma in situ and invasive carcinoma as compared with benign mammary epithelial cells. The loss of ER-ß resulted in abnormal growth of mammary epithelial cells. We have previously shown that the mRNA expression of the ER-ß 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-ß 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-ß methylation status. We also investigated the structural characteristics of the two ER-ß 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-ß promoter methylation by expressing siRNAs in cell lines. Interestingly, by comparing the promoter sequences of ER-ß with other genes known to be epigenetically inactivated in breast cancers, we identified a sequence motif possibly involved in promoter methylation.

This article has been cited by other articles:

				R. Dip, S. Lenz, J.-P. Antignac, B. Le Bizec, H. Gmuender, and H. Naegeli Global gene expression profiles induced by phytoestrogens in human breast cancer cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 161 - 173. [Abstract] [Full Text] [PDF]

				Q. Xue, Z. Lin, Y.-H. Cheng, C.-C. Huang, E. Marsh, P. Yin, M. P Milad, E. Confino, S. Reierstad, J. Innes, et al. Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis Biol Reprod, October 1, 2007; 77(4): 681 - 687. [Abstract] [Full Text] [PDF]