title: Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol.
abstract: OBJECTIVE
  Triphenylethylene (TPE)-like compounds were the first agents to be used in the treatment of metastatic breast cancer in postmenopausal women. Although structurally related to the anti-oestrogen, 4-hydroxytamoxifen, TPEs possess oestrogenic properties in fully oestrogenized breast cancer cells but do not induce apoptosis with short-term treatment in long-term oestrogen-deprived breast cancer cells. This study determined the differential effects of bisphenol, a TPE, on growth and apoptosis based on the modulation of the shape of the ligand-oestrogen receptor complex.
  
  
  METHODS
  Apoptotic flow cytometric studies were used to evaluate apoptosis over time. Proliferation of the breast cancer cells was assessed using DNA quantification and cell cycle analysis. Real-time PCR was performed to quantify mRNA levels of apoptotic genes. Regulation of cell cycle and apoptotic genes was determined using PCR-based arrays.
  
  
  RESULTS
  Bisphenol induced an up-regulation of cell cycle genes similar to those induced by 17β oestradiol (E2 ). Unlike the changes induced by E2 that occur after 24 h, the apoptosis evoked by bisphenol occurred after 4 days, with quantifiable apoptotic changes noted at 6 days. A prolonged up-regulation of endoplasmic reticulum stress and inflammatory stress response genes was observed with subsequent activation of apoptosis-related genes in the second week of treatment with bisphenol.
  
  
  CONCLUSIONS
  The bisphenol: ERα complex induces delayed biological effects on the growth and apoptosis of breast cancer cells. Both the shape of the complex and the duration of treatment control the initiation of apoptosis.
authors.affiliation: Tumor Biology Training Program, Georgetown University, Washington, DC, USA.
authors.forename: I E
authors.initials: IE
authors.lastname: Obiorah
authors.forename: V C
authors.initials: VC
authors.lastname: Jordan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; D004967:Estrogens; D013267:Stilbenes; D004958:Estradiol; C052383:1,1-bis(4-hydroxyphenyl)-2-phenylbut-1-ene
keywords: Oestrogen-induced apoptosis; bisphenol; breast cancer