Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line with tetracycline-dependent ERß expression (T47D-ERß), the effect of a varying intracellular ERa/ERß ratio on genistein-induced gene and protein expression was characterised. Results obtained reveal that in ERa-expressing T47D-ERß cells with inhibited ERß-expression, genistein induces transcriptomics and proteomics signatures pointing at rapid cell growth and migration by dynamic activation of cytoskeleton remodeling. The data reveal an interplay between integrins, focal adhesion kinase (FAK), CDC42 and actin cytoskeleton signaling cascades, occurring upon genistein treatment, in the T47D-ERß breast cancer cells with low levels of ERa and no expression of ERß. In addition, data from our study indicate that ERß-mediated gene and protein expression counteracts ERa-mediated effects, because in T47D-ERß cells expressing ERß and exposed to genistein transcriptomics and proteomics signatures pointing at a clear downregulation of cell growth and induction of cell cycle arrest and apoptosis was demonstrated. These results suggest that ERß decreases cell motility and metastatic potential as well as cell survival of the breast cancer cell line. It is concluded that the effects of genistein on proteomics and transcriptomics endpoints in the T47D-ERß cell model are comparable to those reported previously for estradiol, with the ultimate estrogenic effect being dependent on the relative affinity for both receptors and on the receptor phenotype (ERa/ERß ratio) in the cells or tissue of interes