Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University, Durham, NC 27710, USA.
Mol Cell Endocrinol. 2010 May 5;319(1-2):109-15. doi: 10.1016/j.mce.2010.01.004. Epub 2010 Jan 14.
Extracellular ATP activates purinergic (P(2)) receptors with an increase in intracellular calcium and phosphorylation of MAPK. In this study we have investigated the effect of progesterone/progestin on ATP-induced calcium mobilization and phosphorylation of the kinase ERK in the T47D-Y breast cancer cell line that exhibits no detectable nuclear progesterone receptor expression. Brief pretreatment with progesterone/progestin results in a dose dependent inhibition of ATP-induced intracellular calcium mobilization, and inhibition of ERK phosphorylation. Response to a cell impermeable ligand and inhibition of the response by an inactivating antibody suggests a mechanism of action at the plasma membrane. These results in T47D-Y cells strongly suggest that progesterone can act in a rapid non-nuclear manner to inhibit extracellular ATP effects on intracellular calcium mobilization and ERK activation. This research provides an example of progesterone action in a breast cancer cell line lacking expression of the classical nuclear progesterone receptors.
细胞外 ATP 通过增加细胞内钙和 MAPK 的磷酸化来激活嘌呤能（P2）受体。在这项研究中，我们研究了孕激素/孕酮对 T47D-Y 乳腺癌细胞系中 ATP 诱导的钙动员和激酶 ERK 磷酸化的影响，该细胞系没有检测到核孕激素受体表达。孕激素/孕酮的短暂预处理导致 ATP 诱导的细胞内钙动员和 ERK 磷酸化的剂量依赖性抑制。对细胞不可渗透配体的反应以及失活抗体对反应的抑制表明作用机制发生在质膜上。T47D-Y 细胞中的这些结果强烈表明孕激素可以快速非核方式发挥作用，抑制细胞外 ATP 对细胞内钙动员和 ERK 激活的作用。这项研究提供了孕激素在缺乏经典核孕激素受体表达的乳腺癌细胞系中作用的一个例子。
