Serine protease PRSS23 is upregulated by estrogen receptor α and associated with proliferation of breast cancer cells.
Serine protease PRSS23 is upregulated by estrogen receptor α and associated with proliferation of breast cancer cells.
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DOI：
10.1371/journal.pone.0030397
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chuang YJ
中科院分区：
文献类型：
--
作者：
Chan HS;Chang SJ;Wang TY;Ko HJ;Lin YC;Lin KT;Chang KM;Chuang YJ
丝氨酸蛋白酶PRSS 23是一种新发现的蛋白质，与各种类型癌症的肿瘤进展有关。有趣的是，PRSS 23与雌激素受体α（ERα）共表达，ER α是人类乳腺癌的重要生物标志物和治疗靶点。通过ERα的雌激素信号传导也已知影响细胞增殖、凋亡和存活，其通过调节许多下游效应蛋白的产生促进肿瘤发生。本研究旨在探讨ERα和PRSS 23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显示，在乳腺癌中所有ERα相关蛋白酶中，ERα和PRSS 23之间的基因表达相关性非常显著。然后，我们评估了PRSS 23在56例原发性乳腺癌活检组织和8个癌细胞系中的表达。结果进一步证实了PRSS 23和ERα的共表达，并提供了临床病理学意义。在MCF-7乳腺癌细胞中的体外分析表明，PRSS 23基因的表达是由17β-雌二醇激活的ERα通过与PRSS 23基因上游启动子区的相互作用而诱导的。此外，PRSS 23敲低可抑制雌激素驱动的MCF-7细胞的细胞增殖。我们的研究结果表明PRSS 23可能是雌激素介导的ERα阳性乳腺癌细胞增殖的关键组分。总之，本研究强调了PRSS 23成为乳腺癌研究中新的治疗靶点的潜力。
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.
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影响因子：
5.8
作者：
Ifon ET;Pang AL;Johnson W;Cashman K;Zimmerman S;Muralidhar S;Chan WY;Casey J;Rosenthal LJ
通讯作者：
Rosenthal LJ
影响因子：
4.8
作者：
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通讯作者：
Brugge, JS
影响因子：
11.2
作者：
Jarzab, B;Wiench, M;Swierniak, A
通讯作者：
Swierniak, A
影响因子：
--
作者：
Grisouard, Jean;Medunjanin, Senad;Mayer, Doris
通讯作者：
Mayer, Doris
影响因子：
4.1
作者：
Fritz, WA;Wang, J;Lamartiniere, CA
通讯作者：
Lamartiniere, CA