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Phytoestrogen-Rich Diets Modulate Expression of Brca1 and Brca2 Tumor Suppressor Genes in Mammary Glands of Female Wistar Rats¹

Laboratoire d’Oncologie Moléculaire UMR 484 Institut National de la Santé et de la Recherche Médicale UdA, Centre Jean Perrin, Clermont-Ferrand, Cedex 01 [C. V-S., Y-J. B., D. B-G.]; Groupe Ostéoporose, Unité des Maladies Métaboliques et Micronutriments (U3M), I.N.R.A. de Clermont-Ferrand/Theix, 63122 Saint Genès Champanelle [V. C., C. P., M-N. H., M-J. D., P. L.]; and Service d’Anatomie Pathologique, Hôtel-Dieu, 63005 Clermont-Ferrand [P. D.], France

Phytoestrogens are natural compounds with anticancer, proliferation, differentiation, and chemopreventive effects, for which several mechanisms have been proposed. In the present study, modulation of Brca1 and Brca2 expression by different phytoestrogen-rich diets has been investigated in ovariectomized Wistar rats. Two hundred mammary glands were harvested in three independent experiments. Brca1 and Brca2 mRNAs were quantified by real-time quantitative reverse transcription-PCR, and their proteins by immunohistochemistry. The first experiment compared the influence of different phytoestrogens [flax-seed, isoflavones (IFs), or rutin]. A 10% increase in Brca1 mRNA expression was shown after flax-seed consumption, whereas no variation was noted for Brca2 mRNA, nor for Brca1 and Brca2 proteins. In the second experiment, two soy IFs sources (Novasoy or Soylife) were given at different concentrations to the animals. Only Brca2 mRNA was increased and only at high doses. Finally, the effect of IFs was compared with that of estradiol. An increase in mRNA for both genes was noted after estradiol treatment and with the highest dose of IFs.

In conclusion, our results show that IFs, given in the diet at different doses, are able to increase Brca1 and Brca2 mRNA in ovariectomized female Wistar rat. However, no variation in Brca1 or Brca2 protein expression was demonstrated, whatever the experimental conditions were.

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