Soya phytonutrients act on a panel of genes implicated with BRCA1 and BRCA2 oncosuppressors in human breast cell lines.
Breast cancer is the most common cancer in women and a significant cause of death. Mutations of the oncosuppressor genes BRCA1 and BRCA2 are associated with a hereditary risk of breast cancer, and dysregulation of their expression has been observed in sporadic cases. Soya isoflavones have been shown to inhibit breast cancer in studies in vitro, but associations between the consumption of isoflavone-containing foods and breast cancer risk have varied in epidemiological studies. Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment. The different genes involved in the BRCA1 and BRCA2 pathways (GADD45A, BARD1, JUN, BAX, RB1, ERalpha, ERbeta, BAP1, TNFalpha, p53, p21Waf1/Cip1, p300, RAD51, pS2, Ki-67) were quantified by real-time quantitative RT-PCR, using the TaqMan method and an ABI Prism 7700 Sequence Detector (Applied Biosystems). We observed that, in response to treatment, many of these genes were overexpressed in the breast cancer cell lines (MCF-7 and MDA-MB-231) but not in the dystrophic cell line (MCF10a).
Département d'Oncogénétique du Centre Jean Perrin, INSERM UMR 484-UdA, Centre Biomédical de Recherche et de Valorisation, 28 place Henri Dunant, B.P.38, 63 001 Clermont-Ferrand Cedex 01, France.
Bertrand
B
Caëtano
Ludovic
L
Le Corre
Nassera
N
Chalabi
Laetitia
L
Delort
Yves-Jean
YJ
Bignon
Dominique J
DJ
Bernard-Gallon
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D019398:Genes, BRCA1 / Q000187:drug effects / Q000502:physiology; D024522:Genes, BRCA2 / Q000187:drug effects / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000187:drug effects* / Q000502:physiology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013025:Glycine max / Q000737:chemistry*; D014158:Transcription, Genetic / Q000187:drug effects
D016588:Anticarcinogenic Agents; D007529:Isoflavones; D048789:Phytoestrogens; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C004742:daidzein; D019833:Genistein