The G-protein coupled estrogen receptor (GPER), a proposed tumor suppressor, relays short-term non-genomic responses in target cells and tissues. It frequently undergoes down-modulation in primary tumors of the breast, ovary, and endometrium. Liu and co-workers recently reported loss of GPER expression in colorectal cancer and attributed it to DNA methylation-dependent silencing. We hypothesized that GPER expression is inversely correlated with methylation in the upstream CpG island (upCpGi) in the GPER locus. Methylation in the upCpGi was analysed by bisulfite sequencing and correlated with GPER expression in a panel of colon cancer cell lines. Eight downstream CpGs of the upCpGi was differentially methylated across the cell lines. Methylation in this differentially methylated region (DMR) correlated inversely with GPER expression. Two cell lines, namely SW620 and COLO-320DM, were compared in terms of their viability in response to varying concentrations of G1, a GPER specific agonist. SW-620 cells, which had the least methylated DMR and the highest level of GPER expression, showed significant loss of viability with 1 µM G1. COLO-320DM, which had the most methylated DMR and the lowest level of GPER expression, did not show a significant response to 1 µM G1. At 5 µM G1, SW620 cells showed a greater reduction in viability than COLO-320DM cells. DNA methylation in the DMR is inversely correlated with GPER expression. DNA methylation-dependent silencing of GPER may be, at least in part, the underlying reason behind the loss of estrogen’s oncoprotective effect via GPER in the colon.

G蛋白偶联雌激素受体（GPER）是一种拟议的肿瘤抑制因子，可在靶细胞和组织中传递短期的非基因组应答。它经常在乳腺，卵巢和子宫内膜的原发性肿瘤中经历下调。Liu和他的同事们最近报道了大肠癌中GPER表达的丧失，并将其归因于DNA甲基化依赖性沉默。我们假设GPER表达与GPER基因座上游CpG岛（upCpGi）中的甲基化呈负相关。通过亚硫酸氢盐测序分析了upCpGi中的甲基化，并将其与一组结肠癌细胞系中的GPER表达相关。在整个细胞系中，upCpGi的八个下游CpG被差异甲基化。该差异甲基化区域（DMR）中的甲基化与GPER表达成反比。两个细胞系 分别比较了SW620和COLO-320DM对不同浓度的GPER激动剂G1的活力。具有最低甲基化DMR和最高GPER表达水平的SW-620细胞在1 µM G1时显示出明显的活力丧失。具有最大甲基化DMR和最低GPER表达水平的COLO-320DM对1 µM G1没有明显反应。G1浓度为5 µM时，SW620细胞比COLO-320DM细胞显示出更大的活力降低。DMR中的DNA甲基化与GPER表达呈负相关。GPER的DNA甲基化依赖性沉默可能至少部分是结肠中GPER失去雌激素的抗肿瘤保护作用的根本原因。比较了它们对不同浓度的GPER（一种GPER激动剂）的反应能力。具有最低甲基化DMR和最高GPER表达水平的SW-620细胞在1 µM G1时显示出明显的活力丧失。具有最大甲基化DMR和最低GPER表达水平的COLO-320DM对1 µM G1没有明显反应。G1浓度为5 µM时，SW620细胞比COLO-320DM细胞显示出更大的活力降低。DMR中的DNA甲基化与GPER表达呈负相关。GPER的DNA甲基化依赖性沉默可能至少部分是结肠中GPER失去雌激素的抗肿瘤保护作用的根本原因。比较了它们对不同浓度的GPER（一种GPER激动剂）的反应能力。具有最低甲基化DMR和最高GPER表达水平的SW-620细胞在1 µM G1时显示出明显的活力丧失。具有最大甲基化DMR和最低GPER表达水平的COLO-320DM对1 µM G1没有明显反应。G1浓度为5 µM时，SW620细胞比COLO-320DM细胞显示出更大的活力降低。DMR中的DNA甲基化与GPER表达呈负相关。GPER的DNA甲基化依赖性沉默可能至少部分是结肠中GPER失去雌激素的抗肿瘤保护作用的根本原因。在1 µM G1中显示出明显的活力丧失。具有最大甲基化DMR和最低GPER表达水平的COLO-320DM对1 µM G1没有明显反应。G1浓度为5 µM时，SW620细胞比COLO-320DM细胞显示出更大的活力降低。DMR中的DNA甲基化与GPER表达呈负相关。GPER的DNA甲基化依赖性沉默可能至少部分是结肠中GPER失去雌激素的抗肿瘤保护作用的根本原因。在1 µM G1中显示出明显的活力丧失。具有最大甲基化DMR和最低GPER表达水平的COLO-320DM对1 µM G1没有明显反应。G1浓度为5 µM时，SW620细胞比COLO-320DM细胞显示出更大的活力降低。DMR中的DNA甲基化与GPER表达呈负相关。GPER的DNA甲基化依赖性沉默可能至少部分是结肠中GPER失去雌激素的抗肿瘤保护作用的根本原因。