Transcriptional Profiling of Breast Cancer Cells Exposed to Soy Phytoestrogens After BRCA1 Knockdown With a Whole Human Genome Microarray Approach

Abstract

The estrogen-like properties of the soy phytoestrogens could modulate the estrogen-dependent expression of BRCA1 oncosuppressor, which is highly involved in hereditary and sporadic breast cancer.

In order to better understand the importance of BRCA1 function and the role of other genes involved around BRCA1 in the phytoestrogen pathways, we have exploited the BRCA1-specific knockdown by RNA interference using double stranded small interfering RNA (siRNA) in breast tumor cell lines (MCF-7, MDA-MB-231) and a fibrokystic breast cell line (MCF-10a) and treated with 18.5 μM genistein or 78.5 μM daidzein for 72 h. We used pangenomic microarrays and subsequently TLDA analysis and demonstrated that cumulated BRCA1 knockdown with soy isoflavone supplementations in breast cell lines seems to modulate apoptosis, MAPK pathway, cell communication, xenobiotic metabolism, and sterol metabolism. Also, transient BRCA1 deficiency in breast cell lines significantly diminished or reversed gene expression after phytoestrogen supplementation. We observed that the significant decrease expression of apoptosis-related genes such as BAX, and the increase expression of BCL2, under BRCA1 knockdown condition, were completely reversed after phytoestrogen treatments. These results underlined the role of BRCA1 expression in breast carcinogenesis and suggested that soy phytoestrogen supplementation could play a role in cancer.

ACKNOWLEDGMENTS

N. Chalabi is a postgraduate of the CLARA “Cancéropôle Lyon-Auvergne-Rhône-Alpes,” France. N. Rabiau is recipient of a grant “CIFRE” from Soluscience S.A., Saint-Beauzire, France. We thank “La ligue contre le Cancer.” We thank Timothy Gunnels and Martin Ruocco for facilitating the English translation.