title: Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells.
abstract: BACKGROUND
  The aim of this study was to determine the effects of soy phytoestrogens on the methylation of promoter genes in prostate tumors. The incidence of prostate cancer in Asia is thirty percent lower than in Western countries. Since soy phytoestrogens represent a large portion of the Asian diet, evidence suggests their protective effect against prostate cancer.
  
  
  METHODS
  In three human prostate cancer cell lines, methylation-specific-PCR was used to determine the effect of soy isoflavones (genistein and daidzein), compared to known demethylating agent 5-azacytidine as control in the promoter regions of glutathione S-transferase P1 (GSTP1), Ras association domain family 1 (RASSF1A), ephrin B2 (EPHB2) and breast cancer 1 (BRCA1) genes. In parallel, immunohistochemistry was used to assess the effects of genistein, daidzein and 5-azacytidine treatment on the corresponding protein expression.
  
  
  RESULTS
  All studied promoters, with the exception of that for BRCA1, were strongly methylated without treatment. After treatment by phytoestrogens, demethylation of GSTP1 and EPHB2 promoter regions was observed and an increase in their protein expression was demonstrated by immunohistochemistry.
  
  
  CONCLUSIONS
  Epigenetic modifications of DNA, such as the promoter CpG island demethylation of tumor suppressor genes, might be related to the protective effect of soy on prostate cancer.
authors.affiliation: Département d'Oncogénétique, Centre Jean Perrin, 58 rue Montalembert, BP 392, 63011 Clermont-Ferrand cedex 01, France.
authors.forename: Adam
authors.initials: A
authors.lastname: Vardi
authors.forename: Remy
authors.initials: R
authors.lastname: Bosviel
authors.forename: Nadege
authors.initials: N
authors.lastname: Rabiau
authors.forename: Mawussi
authors.initials: M
authors.lastname: Adjakly
authors.forename: Samir
authors.initials: S
authors.lastname: Satih
authors.forename: Pierre
authors.initials: P
authors.lastname: Dechelotte
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Boiteux
authors.forename: Luc
authors.initials: L
authors.lastname: Fontana
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Laurent
authors.initials: L
authors.lastname: Guy
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Bernard-Gallon
mesh_terms: D019313:BRCA1 Protein / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019398:Genes, BRCA1 / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D048789:Phytoestrogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D036104:Receptor, EphA2 / Q000187:drug effects / Q000235:genetics*; D013025:Glycine max; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D004273:DNA, Neoplasm; D048789:Phytoestrogens; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D036104:Receptor, EphA2