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A genome-wide study of the repressive effects of estrogen receptor beta on estrogen receptor alpha signaling in breast cancer cells.
Karolinska Institutet.ORCID iD: 0000-0002-0602-2062
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2008 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 27, no 7, 1019-1032 p.Article in journal (Refereed) Published
Abstract [en]

Transcriptional effects of estrogen result from its activation of two estrogen receptor (ER) isoforms; ERalpha that drives proliferation and ERbeta that is antiproliferative. Expression of ERbeta in xenograft tumors from the T47D breast cancer cell line reduces tumor growth and angiogenesis. If ERbeta can halt tumor growth, its introduction into cancers may be a novel therapeutic approach to the treatment of estrogen-responsive cancers. To assess the complete impact of ERbeta on transcription, we have made a full transcriptome analysis of ERalpha- and ERbeta-mediated gene regulation in T47D cell line with Tet-Off regulated ERbeta expression. Of the 35 000 genes and transcripts analysed, 4.1% (1434) were altered by ERalpha activation. Tet withdrawal and subsequent ERbeta expression inhibited the ERalpha regulation of 998 genes and, in addition, altered expression of 152 non-ERalpha-regulated genes. ERalpha-induced and ERbeta-repressed genes were involved in proliferation, steroid/xenobiotic metabolism and ion transport. The ERbeta repressive effect was further confirmed by proliferation assays, where ERbeta was shown to completely oppose the ERalpha-E2 induced proliferation. Additional analysis of ERbeta with a mutated DNA-binding domain revealed that this mutant, at least for a quantity of genes, antagonizes ERalpha even more strongly than ERbeta wt. From an examination of the genes regulated by ERalpha and ERbeta, we suggest that introduction of ERbeta may be an alternative therapeutic approach to the treatment of certain cancers.

Place, publisher, year, edition, pages
2008. Vol. 27, no 7, 1019-1032 p.
National Category
Cell and Molecular Biology
Research subject
SRA - Molecular Bioscience
URN: urn:nbn:se:kth:diva-165364DOI: 10.1038/sj.onc.1210712ISI: 000252946300014PubMedID: 17700529ScopusID: 2-s2.0-38949182981OAI: diva2:808127

QC 20150428

Available from: 2015-04-27 Created: 2015-04-27 Last updated: 2015-04-28Bibliographically approved

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