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.
Sogon
Tetsuya
T
Department of Molecular Epidemiology, Hiroshima University Graduate School of Biomedical Sciences, Radiation Effects Research Foundation, 5-2, Hijiyama-park, Minami-ku, Hiroshima 732-0815, Japan.
Masamura
Shigeru
S
Hayashi
Shin-Ichi
S
Santen
Richard J
RJ
Nakachi
Kei
K
Eguchi
Hidetaka
H
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D047628:Estrogen Receptor alpha / Q000235:genetics*; D004967:Estrogens / Q000172:deficiency*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger