In vitro inhibition of SKOV-3 cell migration as a distinctive feature of progesterone receptor membrane component type 2 versus type 1
In vitro inhibition of SKOV-3 cell migration as a distinctive feature of progesterone receptor membrane component type 2 versus type 1
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DOI：
10.1016/j.steroids.2012.09.006
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发表时间：
2012-12-01
期刊：
影响因子：
2.7
通讯作者：
Wendler, Alexandra
中科院分区：
文献类型：
--
作者：
Albrecht, Christian;Huck, Volker;Wendler, Alexandra
黄体酮受体膜成分 2 型 (PGRMC2) 与 PGRMC1 高度同源，PGRMC1 在卵巢癌和其他癌细胞中高表达，据称在化疗耐药中发挥重要作用。尽管 PGRMC1 在体外研究中已被广泛表征，但对 PGRMC2 的了解相对较少。为了确定 PGRMC2 在卵巢癌细胞增殖和迁移中的作用，生成了 PGRMC1 和 2 耗尽且过表达的 SKOV-3 细胞。在细胞-基质阻抗传感研究中，PGRMC2 如果过度表达，会对 SKOV-3 迁移率产生负面影响；相反，资源枯竭与迁移率增加有关。 PGRMC1 在此测定中没有作用。这些效应与 f-肌动蛋白调节或肌动蛋白细胞骨架重组无关。然而，这些高度同源的蛋白质具有许多共同特性。 PGRMC1 和 2 均定位于内质网。据报道，PGRMC1 与细胞色素 P450 蛋白 (CYP) 相互作用，测试了两种不同 CYP 与 PGRMC2 的结合；在人胚胎肾细胞中发现 PGRMC2 与 CYP3A4 和 CYP21A2 存在稳定的相互作用。对于两种 PGRMC 类型，细胞活力测定显示 SKOV-3 在过表达和耗尽细胞中的存活率没有显着差异。 PGRMC2 似乎对顺铂的细胞凋亡作用或孕酮的抗细胞凋亡作用（已报道的 PGRMC1）也没有任何影响。与 PGRMC1 相比，SKOV-3 细胞中 PGRMC2 的蛋白水平通过顺铂 (30-60 μM) 处理而降低。总之，我们首次证明 PGRMC2 在体外抑制 SKOV-3 卵巢癌细胞的迁移。 (c) 2012 Elsevier Inc. 保留所有权利。
Progesterone receptor membrane component type 2 (PGRMC2) is strongly homologous to PGRMC1 which is highly expressed in ovarian cancer and other cancer cells and was claimed to play an important role in chemotherapy resistance. Whereas PGRMC1 has been extensively characterized in in vitro studies, comparably little is known about PGRMC2. To determine PGRMC2's role in ovarian cancer cell proliferation and mobility PGRMC1- and 2-depleted and -overexpressing SKOV-3 cells were generated. In electric cell-substrate impedance sensing studies, PGRMC2 negatively affects SKOV-3 migration rate if overexpressed; oppositely, depletion was associated with an increased migration rate. PGRMC1 had no effect in this assay. These effects were not associated with f-actin regulation or actin cytoskeleton reorganization. Yet, these highly homologous proteins share many properties. Both PGRMC1 and 2 are localized to the endoplasmic reticulum. As PGRMC1 was reported to interact with cytochrome P450 proteins (CYP) binding of two different CYPs to PGRMC2 was tested; a stable interaction of PGRMC2 with CYP3A4 and CYP21A2 was found in human embryonic kidney cells. For both PGRMC types, cell viability assays revealed no significant differences of SKOV-3 survival in overexpressing and depleted cells. PGRMC2 also does not seem to have any influence on the apoptotic effect of cisplatin or the antiapoptotic effect of progesterone which had been reported for PGRMC1. In contrast to PGRMC1, protein levels of PGRMC2 in SKOV-3 cells are reduced by treatment with cisplatin (30-60 mu M). In conclusion, we show for the first time that PGRMC2 inhibits migration of SKOV-3 ovarian cancer cells in vitro. (c) 2012 Elsevier Inc. All rights reserved.