Chronic cadmium exposure decreases the dependency of MCF7 breast cancer cells on ERa

To understand how chronic cadmium exposure alters the dependency of ERa in terms of gene expression, we transiently silenced ERa using ICI, an antiestrogen that promotes the degradation of ERa. MCF7 and cadmium-adapted cells (Cd7 and Cd12) were treated with ICI to mediate the degradation of ERa, and a nonbiased global gene expression analysis was conducted using RNA-seq. MCF7 shared 67.3% and 59.5% of the DE genes with Cd7 and Cd12 cells, respectively, suggesting that ERa continues to play an important role in regulating the expression of genes following chronic cadmium exposure. 138 ERE genes (76.7%) were shared by all three cell lines, in that expression changed in the same direction (either up- or downregulated). For the estrogen-responsive genes, 428 (53.6%) of the 799 genes were altered in the same direction in all three cell lines. These findings show that while a majority of ERE genes responded in the same manner to loss of ERa, more variability existed within the estrogen-responsive genes. Collectively, these results indicate that while chronic cadmium exposure leads to genome-wide transcriptional changes, ERa remains important for regulating the expression of genes and maintaining the malignant phenotypes associated with breast cancer progression. Overall design: Examination of mRNA expression, specifically of estrogen-regulated and estrogen-responsive genes, in breast cancer cells chronically exposed to cadmium.