@article{StraubeBrandensteinGeisbueschetal.2013,
  author    = {Julia Straube and Melanie von Brandenstein and Christina Geisbuesch and Luca Ozretic and Reinhard Depping and Jochen W. U. Fries},
  title     = {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},
  series   = {Life Sciences},
  volume    = {93},
  number    = {25–26},
  publisher = {Elsevier},
  issn      = {0024-3205},
  doi       = {10.1016/j.lfs.2013.12.042},
  url       = {https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-10826},
  pages     = {e3 -- e4},
  year      = {2013},
  abstract  = {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.},
  language  = {en}
}