Regulation of ER(estrogen receptor) gene expression in the genesis and development of breast cancer

We studied the regulation of ER alpha gene expression in terms of transcriptional regulation and DNA-methylation in human breast cancer. In cancer, levels of ER alpha mRNA transcribed from a distal promoter (promoter B) remarkably correlated to the protein levels. The binding protein(ERBF-1) of an important cis-element, which we identified, was exclusively expressed in the cells expressing ER alpha, indicating its important role in the enhanced expression of ER alpha in breast cancer. Furthermore, loss of ER alpha expression is the most important event in development of breast cancer. We found that methylation of two promoters of ER alpha was inversely associated with the gene expression in human breast cancer. Specifically, methylation of promoter B suppressed ER alpha expression, and demethylating treatment recovered it. Both methylation of ER alpha gene and modification of transcription by certain trans-acting factors are important for the regulation of ER alpha expression during breast carcinogenesis.