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.
Document Type: | Article |
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Language: | English |
Author: | Julia Straube, Melanie von Brandenstein, Christina Geisbuesch, Luca Ozretic, Reinhard Depping, Jochen W. U. Fries |
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 |
Copyright: | ©2013 The Authors under CC BY-NC-ND license. |
Note: | Abstracts from the Thirteenth International Conference on Endothelin (ET-13), Tokyo, September 8-11, 2013 |
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): | Creative Commons - CC BY-NC-ND - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0 |