@article{WeissenbornIgnatovOcheletal.2014,
  author    = {Weissenborn, Christine and Ignatov, Tanja and Ochel, Hans-Joachim and Costa, Serban Dan and Zenclussen, Ana Claudia and Ignatova, Zoya and Ignatov, Atanas},
  title     = {GPER functions as a tumor suppressor in triple-negative breast cancer cells},
  series = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  volume    = {140},
  journal   = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  number    = {5},
  publisher = {Springer},
  address   = {New York},
  issn      = {0171-5216},
  doi       = {10.1007/s00432-014-1620-8},
  pages     = {713 -- 723},
  year      = {2014},
  abstract  = {We investigated the role of GPER as a potential tumor suppressor in triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468 using cell cycle analysis and apoptosis assay. The constitutive activity of GPER was investigated. GPER-specific activation with G-1 agonist inhibited breast cancer cell growth in concentration-dependent manner via induction of the cell cycle arrest in G2/M phase, enhanced phosphorylation of histone H3 and caspase-3-mediated apoptosis. Analysis of the methylation status of the GPER promoter in the triple-negative breast cancer cells and in tissues derived from breast cancer patients revealed that GPER amount is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Furthermore, GPER expression was induced by stress factors, such as radiation, and GPER amount inversely correlated with the p53 expression level. Overall, our results establish the protective role in breast cancer tumorigenesis, and the cell surface expression of GPER makes it an excellent potential therapeutic target for triple-negative breast cancer.},
  language  = {en}
}
@phdthesis{Mabrok2013,
  author    = {Mabrok, Hoda Hussein Bakr},
  title     = {Protective role of lignan-converting bacteria on chemically-induced breast cancer in gnotobiotic rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-64933},
  school      = {Universit{\"a}t Potsdam},
  year      = {2013},
  abstract  = {Enterolignans (enterodiol and enterolactone) exhibit structural similarity to estradiol and have therefore been hypothesized to modulate hormone related cancers such as breast cancer. The bioactivation of the plant lignan secoisolariciresinol diglucoside (SDG) requires the transformation by intestinal bacteria including the deglycosylation of SDG to secoisolariciresinol (SECO) followed by demethylation and dehydroxylation of SECO to enterodiol (ED). Finally, ED is dehydrogenated to enterolactone (EL). It is unclear whether the bacterial activation of SDG to ED and EL is crucial for the cancer preventing effects of dietary lignans. The possible protective effect of bacterial lignan transformation on a 7,12 dimethylbenz(a)anthracene (DMBA)-induced breast cancer in gnotobiotic rats was investigated. Germ-free rats were associated with a defined lignan-converting consortium (Clostridium saccharogumia, Blautia producta, Eggerthella lenta, and Lactonifactor longoviformis). The rats colonized with lignan-converting bacteria consortium (LCC) were fed a lignan-rich flaxseed diet and breast cancer was chemical induced. Identically treated germ-free rats served as control. All bacteria of the consortium successfully colonized the intestine of the LCC rats. The plant lignan SDG was converted into the enterolignans ED and EL in the LCC rats but not in the germ-free rats. This transformation did not influence cancer incidence but significantly decreased tumor numbers per tumor-bearing rat, and tumor size. Cell proliferation was significantly inhibited and apoptosis was significantly induced in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERα and ERβ) and G-coupled protein receptor 30 (GPR30). Similar findings were observed for both insulin-like growth factor 1 (IGF-1) and epidermal growth factor receptor (EGFR) genes involved in tumor growth. Proteome analysis revealed that 24 proteins were differentially expressed in tumor tissue from LCC and germ-free. RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1) and poly(rC)-binding protein 1 (PBCP1) were down-regulated by 3.2- and 2.0-fold, respectively. These proteins are associated with cell proliferation. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione (non-enzymatic antioxidant) and malondialdehyde (oxidative stress marker) did not differ between the groups. In conclusion, the bacterial conversion of plant lignan to enterolignans beneficially influences their anti-cancer effect. However, the mechanisms involved in these effects remain elusive.},
  language  = {en}
}