G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells
G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells
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DOI：
10.1210/en.2001-211445
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发表时间：
2002-09-01
期刊：
影响因子：
4.8
通讯作者：
Ylikomi, T
中科院分区：
文献类型：
--
作者：
Ahola, TM;Manninen, T;Ylikomi, T
孕激素如何影响乳腺生长的问题是有争议的，并且控制激素作用的机制仍然是未知的。我们以前已经表明，G蛋白偶联受体30（GPR 30）是一个孕激素靶基因，其表达与孕激素诱导的乳腺癌细胞生长抑制相关。在这项研究中，我们调查GPR 30在调节细胞增殖和介导孕激素诱导的生长抑制中的作用。当白藜芦醇不能抑制MCF-7细胞的生长，而是刺激生长时，GPR 30下调。以这种方式，珠蛋白对增殖的抑制或刺激作用与GPR 30的表达水平相关。GPR 30的瞬时表达导致细胞增殖的显著抑制，而不依赖于雌激素治疗。GPR 30反义核酸用于评估GPR 30表达在孕激素诱导的生长抑制中的作用。反义GPR 30 mRNA表达减少刺激生长。有趣的是，GPR 30反义消除了孕激素和孕酮的生长抑制作用。事实上，白细胞介素诱导1）细胞增殖减少，2）G1期阻滞，3）细胞周期蛋白D1的下调减少。这些数据表明，孤儿受体，GPR 30，是很重要的抑制作用的resistin的生长。
The issue of how progesterone affects mammary gland growth is controversial, and the mechanism governing the effects of the hormone remains mostly unknown. We have previously shown that G protein-coupled receptor 30 (GPR30) is a progestin target gene whose expression correlates with progestin-induced growth inhibition in breast cancer cells. In this study, we investigate the role of GPR30 in regulating cell proliferation and mediating progestin-induced growth inhibition. When progestin failed to inhibit the growth of MCF-7 cells and instead stimulated growth, GPR30 was down-regulated. In this way, the inhibitory or stimulatory affects that progestin has on proliferation correlated with the level of expression of GPR30. Transient expression of GPR30 resulted in a marked inhibition of cell proliferation independent of estrogen treatment. GPR30 antisense was used to evaluate the role of GPR30 expression in progestin-induced growth inhibition. A diminished GPR30 mRNA expression by the antisense stimulated growth. Interestingly, GPR30 antisense abrogated the growth inhibitory effect of progestin and progesterone. Indeed, progestin induced 1) a reduction in cell proliferation, 2) G1-phase arrest, and 3) down-regulation of cyclin D1 was diminished. These data suggest that the orphan receptor, GPR30, is important for the inhibitory effect of progestin on growth.