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丝氨酸蛋白酶 PRSS23 受雌激素受体 α 上调,并与乳腺癌细胞增殖相关。

Serine protease PRSS23 is upregulated by estrogen receptor α and associated with proliferation of breast cancer cells.

机构信息

Department of Medical Science, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, ROC.

出版信息

PLoS One. 2012;7(1):e30397. doi: 10.1371/journal.pone.0030397. Epub 2012 Jan 23.

Abstract

Serine protease PRSS23 is a newly discovered protein that has been associated with tumor progression in various types of cancers. Interestingly, PRSS23 is coexpressed with estrogen receptor α (ERα), which is a prominent biomarker and therapeutic target for human breast cancer. Estrogen signaling through ERα is also known to affect cell proliferation, apoptosis, and survival, which promotes tumorigenesis by regulating the production of numerous downstream effector proteins.In the present study, we aimed to clarify the correlation between and functional implication of ERα and PRSS23 in breast cancer. Analysis of published breast cancer microarray datasets revealed that the gene expression correlation between ERα and PRSS23 is highly significant among all ERα-associated proteases in breast cancer. We then assessed PRSS23 expression in 56 primary breast cancer biopsies and 8 cancer cell lines. The results further confirmed the coexpression of PRSS23 and ERα and provided clinicopathological significance. In vitro assays in MCF-7 breast cancer cells demonstrated that PRSS23 expression is induced by 17β-estradiol-activated ERα through an interaction with an upstream promoter region of PRSS23 gene. In addition, PRSS23 knockdown may suppress estrogen-driven cell proliferation of MCF-7 cells.Our findings imply that PRSS23 might be a critical component of estrogen-mediated cell proliferation of ERα-positive breast cancer cells. In conclusion, the present study highlights the potential for PRSS23 to be a novel therapeutic target in breast cancer research.

摘要

丝氨酸蛋白酶 PRSS23 是一种新发现的蛋白质,与多种癌症的肿瘤进展有关。有趣的是,PRSS23 与雌激素受体 α(ERα)共表达,ERα 是人类乳腺癌的重要生物标志物和治疗靶点。通过 ERα 的雌激素信号也已知会影响细胞增殖、凋亡和存活,通过调节许多下游效应蛋白的产生来促进肿瘤发生。在本研究中,我们旨在阐明 ERα 和 PRSS23 在乳腺癌中的相关性及其功能意义。对已发表的乳腺癌微阵列数据集的分析表明,在乳腺癌中所有与 ERα 相关的蛋白酶中,ERα 和 PRSS23 之间的基因表达相关性非常显著。然后,我们评估了 56 个原发性乳腺癌活检和 8 个癌细胞系中 PRSS23 的表达。结果进一步证实了 PRSS23 和 ERα 的共表达,并提供了临床病理意义。在 MCF-7 乳腺癌细胞中的体外实验表明,PRSS23 的表达通过与 PRSS23 基因上游启动子区域的相互作用,被 17β-雌二醇激活的 ERα 诱导。此外,PRSS23 敲低可能会抑制 MCF-7 细胞中雌激素驱动的细胞增殖。我们的发现表明,PRSS23 可能是 ERα 阳性乳腺癌细胞中雌激素介导的细胞增殖的关键组成部分。总之,本研究强调了 PRSS23 作为乳腺癌研究中一种新的治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8269/3264607/6ae3c4702a3b/pone.0030397.g001.jpg

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