title: Antiestrogens suppress effects of transforming growth factor-β in breast cancer cells via the signaling axis estrogen receptor-α and Y-box Binding Protein-1.
abstract: BACKGROUND
  Multifunctional Y-box Binding Protein-1 (YB1) is correlated with a poor outcome in breast cancer. We found YB1 expression to be regulated by antiestrogens commonly used in the hormonal therapy of breast cancer and known as activators of Transforming Growth Factor-β (TGFβ). Thus, a putative influence of YB1 on TGFβ signaling should be investigated.
  
  
  METHODS
  The effect of YB1 on TGFβ signaling was monitored by expression analysis and reporter gene assays in breast cancer cells overexpressing YB1 and treated with antiestrogens.
  
  
  RESULTS
  Antiestrogen-mediated inhibition of estrogen receptor-α led to a suppression of YB1 protein synthesis. On the other hand, YB1 was found to be an enhancer of TGFβ signaling.
  
  
  CONCLUSIONS
  High levels of YB1 expression lead to a stimulation of TGFβ pathways, thereby counteracting antihormonal breast cancer therapy and representing a putative resistance mechanism.
authors.affiliation: Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Simone L
authors.initials: SL
authors.lastname: Popp
authors.forename: Christian
authors.initials: C
authors.lastname: Joffroy
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Buck
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D013629:Tamoxifen / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D016212:Transforming Growth Factor beta; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol
keywords: Estrogen receptor; Y-box binding protein-1; antiestrogen; resistance; transforming growth factor β