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Tamoxifen treatment in breast cancer induces a cytoplasmic complex consisting of endothelin-1, estrogen receptors, and Tamoxifen leading to nuclear transmigration, and transcription of target genes involved in metastatic spread

  • Tamoxifen therapy of invasive breast cancer has been associated with increased levels of endothelin-1 (ET-1) so that an endothelin-1 receptor (ETR) blockade has been suggested as a new therapeutic approach. This study analyzed the relationship between Tamoxifen and ET-1 signalling in invasive breast cancer. Using paraffinized tissue from 50 randomly chosen cases of invasive and in-situ ductal carcinoma from our archive, the expression of ETRs was analyzed by immune histology. ETRs were regularly detectable in normal breast tissue, but rarely in adjacent tumor areas (3/50 cases). By immunoprecipitation, a complex was found consisting of ET-1, estrogen receptors and Tamoxifen. Consequently, transcription of several target genes of ET-1 and estrogen receptors was detectable (interleukin-6, wnt-11 and a vimentin spliceform). In particular, the combination of Tamoxifen, ET-1, and estrogen receptors induced further increasing levels of these target genes. Some of these genes have been found upregulated in metastatically spreading breast cancer cells. We conclude: i) ETRs do not play a role in invasive or in-situ ductal breast cancer; ii) estrogen receptors and Tamoxifen build a complex with ET-1; and iii) upregulated transcription of target genes by ET-1–estrogen receptor–Tamoxifen complex may negatively influence breast cancer prognosis. These results indicate a role for ET-1 in Tamoxifen treated breast cancer patients leading to a potentially worsening prognosis.

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Metadaten
Document Type:Article
Language:English
Parent Title (English):Life Sciences
Volume:93
Issue:25–26
First Page:e3
Last Page:e4
ISSN:0024-3205
URN:urn:nbn:de:hbz:1044-opus-10826
DOI:https://doi.org/10.1016/j.lfs.2013.12.042
Publisher:Elsevier
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2014/01/20
Note:
Abstracts from the Thirteenth International Conference on Endothelin (ET-13), Tokyo, September 8-11, 2013
Note:
©2013 The Authors under CC BY-NC-ND license.
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2015/04/02
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0