title: Promoting E2F1-mediated apoptosis in oestrogen receptor-α-negative breast cancer cells.
abstract: BACKGROUND
  Because oestrogen receptor α (ERα) regulates E2F1 expression to mediate tamoxifen resistance in ERα-positive breast cancer cells, we aimed to define the possible roles of ERα and E2F1 in promoting the resistance of ERα-negative breast cancer cells to 4-hydroxy-tamoxifen (4OHT).
  
  
  METHODS
  This study utilised conventional techniques to demonstrate the effects of 4OHT on the expression of ERα and E2F1 and also examined the individual and combined effects of 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) on the oestrogen-negative MDA-MB-231 breast cancer cell line using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and confocal microscopy.
  
  
  RESULTS
  Despite the ERα-negative status of the MDA-MB-231 cells, we observed that 4OHT efficiently up-regulated ERα in these cells and that this upregulation promoted E2F1-mediated cell growth. Because E2F1 plays a dual role in cell growth/apoptosis, we designed a therapy incorporating TMCG/DIPY to take advantage of the elevated E2F1 expression in these 4OHT-treated cells. 4OHT enhances the toxicity of TMCG/DIPY in these ERα-negative breast cancer cells.
  
  
  CONCLUSIONS
  Because TMCG/DIPY treatment modulates the methylation status/stability of E2F1, the results demonstrate that therapies targeting the epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may result in efficient E2F1-mediated cell death.
authors: Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, 30100 Espinardo, Murcia, Spain. fermontenegro@um.es.
authors: María F
authors: MF
authors: Montenegro
authors: María Del Mar
authors: Mdel M
authors: Collado-González
authors: María Piedad
authors: MP
authors: Fernández-Pérez
authors: Manel B
authors: MB
authors: Hammouda
authors: Lana
authors: L
authors: Tolordava
authors: Mariam
authors: M
authors: Gamkrelidze
authors: José Neptuno
authors: JN
authors: Rodríguez-López
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C559677:3-O-(3,4,5-trimethoxybenzoyl)catechin; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen; C016601:afimoxifene; D004176:Dipyridamole; D002392:Catechin