Soy phytoestrogens modify DNA methylation of GSTP1, RASSF1A, EPH2 and BRCA1 promoter in prostate cancer cells.
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.
Vardi
Adam
A
Département d'Oncogénétique, Centre Jean Perrin, 58 rue Montalembert, BP 392, 63011 Clermont-Ferrand cedex 01, France.
Bosviel
Remy
R
Rabiau
Nadege
N
Adjakly
Mawussi
M
Satih
Samir
S
Dechelotte
Pierre
P
Boiteux
Jean-Paul
JP
Fontana
Luc
L
Bignon
Yves-Jean
YJ
Guy
Laurent
L
Bernard-Gallon
Dominique J
DJ
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*
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