Soya phytonutrients act on a panel of genes implicated with BRCA1 and BRCA2 oncosuppressors in human breast cell lines

• Published in: British journal of nutrition 2006-02, Vol.95 (2), p.406-413
• Main Authors: Caetano, B, Le Corre, L, Chalabi, N, Delort, L, Bignon, Y.J, Bernard-Gallon, D.J
• Format: Article
• Language: English
• Subjects: anticarcinogenic activity; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; breast neoplasms; Breast Neoplasms - genetics; Cell Line, Tumor; cell lines; daidzein; DNA primers; epidemiology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; gene overexpression; genes; Genes, BRCA1 - drug effects; Genes, BRCA1 - physiology; Genes, BRCA2 - drug effects; Genes, BRCA2 - physiology; Genes, Tumor Suppressor - drug effects; Genes, Tumor Suppressor - physiology; genistein; Genistein - pharmacology; Glycine max - chemistry; Humans; inheritance (genetics); inhibitors; Isoflavones - pharmacology; molecular sequence data; neoplasms; nutrition-genotype interaction; phytochemicals; Phytoestrogens - pharmacology; quantitative trait loci; reverse transcriptase polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction - methods; risk factors; RNA, Messenger - genetics; RNA, Neoplasm - genetics; soy protein; Transcription, Genetic - drug effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1079/BJN20051640

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 microgram/ml) and daidzein (20 microgram/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, p21(Waf1/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).