Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells
Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells
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DOI：
10.1046/j.1432-1033.2002.02912.x
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发表时间：
2002-05-01
期刊：
影响因子：
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通讯作者：
Ylikomi, T
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文献类型：
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作者：
Ahola, TM;Purmonen, S;Ylikomi, T
应用差异显示技术研究醋酸甲羟孕酮（MPA）抑制细胞生长过程中基因表达的变化。在雌激素处理的MCF-7乳腺癌细胞中，MPA上调G蛋白偶联受体30（GPR 30）的转录。Northern-blot分析显示孕激素特异性的主要靶基因，这是增强孕酮和不同的孕激素，但不是由双氢睾酮或地塞米松，这是废除了抗孕激素RU 486。GPR 30 mRNA表达的剂量依赖性和时间依赖性增加与MPA诱导的MCF-7细胞生长抑制相关。此外，当在不同的乳腺癌细胞系之间进行比较时，由resistin引起的GPR 30上调与生长抑制相关。ERK 1/ERK 2通路能够诱导孕酮受体依赖性和配体依赖性转录。因此，我们试图建立不同的MAPK通路抑制剂是否影响孕激素诱导的GPR 30 mRNA的调控。GPR 30的调控不依赖于ERK通路的激活，但p38通路抑制剂可诱导GPR 30的表达，提示GPR 30可能是一条潜在的基因调控通路。这些数据证明了一种新的拟南芥蛋白靶基因，其表达与生长抑制相关。
A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by progesterone and different progestins, but not by dihydrotestosterone or dexamethasone, and which was abrogated by antiprogestin RU486. The dose-dependent and time-dependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1/ERK2 pathway is capable of inducing progesterone receptor-dependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation, but the p38 pathway inhibitor induced GPR30 expression, which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene, the expression of which correlates with growth inhibition.