Demethylation of promoter C region of estrogen receptor alpha gene is correlated with its enhanced expression in estrogen-ablation resistant MCF-7 cells.

Long-term estrogen deprivation (LTED) MCF-7 cells showing estrogen-independent growth, express estrogen receptor (ER) alpha at a much higher level than wild-type MCF-7 cells. Enhanced expression of ERalpha associated with partial localization of ERalpha to the plasma membranes in LTED cells is thought to be an important step for acquisition of estrogen-ablation resistance. In this study, we compared the regulation of ERalpha gene expression between wild type and LTED cells, examining the usage of the promoters A and C as well as their methylation status. We found that transcription from the promoter C was drastically enhanced in LTED cells, compared with that in wild-type cells. Furthermore, the promoter C region was highly unmethylated in LTED cells, but partially methylated in wild-type cells. Our findings imply that demethylation of promoter C region in the ERalpha gene is in part responsible for the enhanced expression of ERalpha gene in LTED cells.