Biology Research Institute of the United Laboratories International Holdings Limited, 528467, Zhuhai, China.
Med Oncol. 2010 Dec;27(4):1340-5. doi: 10.1007/s12032-009-9386-6. Epub 2009 Dec 15.
A mimic of phosphorylated prolactin (S179D PRL) inhibits mouse normal mammary HC11 cell proliferation through the upregulation of the vitamin D receptor (VDR) and p21. Here, we investigated whether S179D PRL also inhibited growth of human breast cancer MCF7 cells via VDR and p21. Western blots showed that S179D PRL upregulated VDR and p21 after the cells were incubated with S179D PRL for 3 days. These effects were blocked by the MAP kinase blocker PD98059 (25 μM), indicating that MAPK plays a role in VDR and p21 upregulation. To confirm whether VDR contributes to p21 upregulation, we used two constructs that express luciferase. One (p21 VDRE Luc) has the vitamin D response element (VDRE) in the p21 promoter region; the other (p21 NO-VDRE Luc) does not. The results show that S179D PRL upregulated p21 VDRE Luc activity in p21 VDRE Luc-transfected cells more than in p21 NO-VDRE-transfected cells, indicating that S179D PRL upregulated p21 via VDR. A cell proliferation assay showed that S179D PRL inhibits cell proliferation in a dose-dependent manner.
一种磷酸化催乳素（S179D PRL）的模拟物通过上调维生素 D 受体（VDR）和 p21 抑制正常小鼠乳腺 HC11 细胞增殖。在这里，我们研究了 S179D PRL 是否也通过 VDR 和 p21 抑制人乳腺癌 MCF7 细胞的生长。Western blot 显示，S179D PRL 在孵育 S179D PRL 3 天后上调 VDR 和 p21。这些作用被 MAP 激酶抑制剂 PD98059（25μM）阻断，表明 MAPK 在 VDR 和 p21 的上调中起作用。为了确认 VDR 是否有助于 p21 的上调，我们使用了两种表达荧光素酶的构建体。一个（p21 VDRE Luc）在 p21 启动子区域具有维生素 D 反应元件（VDRE）；另一个（p21 NO-VDRE Luc）没有。结果表明，S179D PRL 在 p21 VDRE Luc 转染细胞中比在 p21 NO-VDRE 转染细胞中上调 p21 VDRE Luc 活性更多，表明 S179D PRL 通过 VDR 上调 p21。细胞增殖试验表明，S179D PRL 以剂量依赖的方式抑制细胞增殖。
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