TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Straube, Julia
A1  - Brandenstein, Melanie von
A1  - Geisbuesch, Christina
A1  - Ozretic, Luca
A1  - Depping, Reinhard
A1  - Fries, Jochen W. U.
T1  - 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
JF  - Life Sciences
N2  - 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.
Y1  - 2013
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-10826
SN  - 0024-3205
SS  - 0024-3205
U6  - https://doi.org/10.1016/j.lfs.2013.12.042
DO  - https://doi.org/10.1016/j.lfs.2013.12.042
N1  - Abstracts from the Thirteenth International Conference on Endothelin (ET-13), Tokyo, September 8-11, 2013
VL  - 93
IS  - 25–26
SP  - e3
EP  - e4
PB  - Elsevier
ER  -