Enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in breast cancer and plays an important role in maintaining the cell proliferative capacity. However, the mechanisms underlying the transcriptional regulation of EZH2 in estrogen receptor (ER)-positive breast cancer cells remain unclear. The antitumor effects of resveratrol have been reported. However, whether EZH2 was involved in these effects needs further exploration. Here, we showed that EZH2 is required for estrogen-induced cell proliferation in ER-positive breast cancer. Exposure to 17β-estradiol (E₂) upregulated EZH2 via ERα signaling, and this effect was blocked by U0126, a MEK inhibiter. Resveratrol inhibited the proliferation and colony formation in ER-positive breast cancer cells and downregulated EZH2 through inhibition of phospho-ERK1/2. These findings indicated that ERK1/2 and ER signaling–mediated EZH2 upregulation is crucial for the proliferation of ER-positive breast cancer cells. The suppression of EZH2 expression by ERK1/2 dephosphorylation is important for the antiproliferative activities of resveratrol against ER-positive breast cancer cells.

中文翻译：

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白藜芦醇通过调节 ERK1/2 信号传导抑制 EZH2，从而抑制雌激素受体阳性乳腺癌细胞的增殖。

zeste 同系物 2 (EZH2) 增强子在乳腺癌中经常过度表达，并在维持细胞增殖能力方面发挥重要作用。然而，EZH2 在雌激素受体 (ER) 阳性乳腺癌细胞中转录调控的机制仍不清楚。白藜芦醇的抗肿瘤作用已有报道。然而，EZH2是否参与了这些影响还需要进一步探索。在这里，我们发现 EZH2 是雌激素诱导的 ER 阳性乳腺癌细胞增殖所必需的。暴露于 17β-雌二醇 (E ₂) 通过 ERα 信号上调 EZH2，这种作用被 MEK 抑制剂 U0126 阻断。白藜芦醇抑制 ER 阳性乳腺癌细胞的增殖和集落形成，并通过抑制磷酸化 ERK1/2 下调 EZH2。这些发现表明 ERK1/2 和 ER 信号介导的 EZH2 上调对于 ER 阳性乳腺癌细胞的增殖至关重要。通过 ERK1/2 去磷酸化抑制 EZH2 表达对于白藜芦醇对 ER 阳性乳腺癌细胞的抗增殖活性很重要。