Sogon Tetsuya, Masamura Shigeru, Hayashi Shin-Ichi, Santen Richard J, Nakachi Kei, Eguchi Hidetaka
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.
J Steroid Biochem Mol Biol. 2007 Jun-Jul;105(1-5):106-14. doi: 10.1016/j.jsbmb.2006.12.104. Epub 2007 May 16.
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.
长期雌激素剥夺（LTED）的MCF-7细胞呈现出雌激素非依赖性生长，其雌激素受体（ER）α的表达水平比野生型MCF-7细胞高得多。ERα表达增强且在LTED细胞中部分定位于质膜，这被认为是获得雌激素消融抗性的重要步骤。在本研究中，我们比较了野生型和LTED细胞中ERα基因表达的调控情况，研究了启动子A和C的使用及其甲基化状态。我们发现，与野生型细胞相比，LTED细胞中启动子C的转录显著增强。此外，启动子C区域在LTED细胞中高度未甲基化，但在野生型细胞中部分甲基化。我们的研究结果表明，ERα基因启动子C区域的去甲基化部分导致了LTED细胞中ERα基因表达的增强。
