Proline-, glutamic acid–, leucine-rich protein 1 (PELP1) is a novel estrogen receptor (ER) coregulator, demonstrated distinctive characters from other ERα coregulators, and has been suggested to be involved in metastasis of several cancers. In ERα-positive breast cancer, PELP1 overexpression enhanced ruffles and filopodium-like structure stimulated by estradiol (E₂) through extranuclear cell signaling transduction hereby increased cell motility. However, whether PELP1 is also involved in extracellular matrix remodeling of ERα-positive breast cancer cells is still unknown. In this study, we investigated the role of PELP1 in E₂-induced MMP-9 expression and the underlined mechanism. The results demonstrated the following: E₂-induced ERα-positive MCF-7 breast cancer cell MMP-9 mRNA and protein expression in a rapid response and concentration-dependent manner. Knocked down PELP1 significantly suppressed E₂-induced MMP-9 expression. E₂-bovine serum albumin (BSA), a large molecular membrane-impenetrable conjugate of E₂, can also upregulate MMP-9 protein expression in MCF-7, and the action of E₂-BSA can be abolished by PI3K inhibitor LY294002; treating MCF-7 simultaneously with PELP1-shRNA and LY294002 did not show synergetic inhibitory effect on E₂-BSA-induced MMP-9 expression. Our results indicated that estrogen-induced MMP-9 expression in ER-positive breast cancer cells may be through PELP1-mediated PI3K/Akt signaling pathway.

中文翻译：

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在 ERα 阳性乳腺癌细胞中，雌二醇通过 PELP1 介导的膜启动信号传导诱导 MMP-9 表达。

富含脯氨酸、谷氨酸、亮氨酸的蛋白 1 (PELP1) 是一种新型雌激素受体 (ER) 共调节因子，表现出与其他 ERα 共调节因子不同的特征，并被认为参与多种癌症的转移。_{在ERα阳性乳腺癌中，PELP1过表达增强了雌二醇（E 2}）通过核外信号转导刺激的褶边和丝状足样结构，从而增加了细胞运动性。然而，PELP1是否也参与ERα阳性乳腺癌细胞的细胞外基质重塑尚不清楚。_{在本研究中，我们研究了PELP1在E 2}诱导的M​​MP-9表达中的作用及其机制。结果表明：E ₂以快速反应和浓度依赖性方式诱导ERα阳性MCF-7乳腺癌细胞MMP-9 mRNA和蛋白表达。敲低PELP1显着抑制E ₂诱导的M​​MP-9表达。E _{2 -牛血清白蛋白(BSA)是E 2}的大分子膜不可穿透的缀合物，也可以上调MCF-7中MMP-9蛋白的表达，并且E ₂ -BSA的作用可以被PI3K抑制剂LY294002消除；_{同时用PELP1-shRNA和LY294002处理MCF-7对E 2} -BSA诱导的MMP-9表达没有表现出协同抑制作用。我们的结果表明雌激素诱导ER阳性乳腺癌细胞中MMP-9的表达可能是通过PELP1介导的PI3K/Akt信号通路。