Skip Regulates TGF- β 1-Induced Extracellular Matrix Degrading Proteases Expression in Human PC-3 Prostate Cancer Cells.

IF 2.3 Q3 ONCOLOGY
Prostate Cancer Pub Date : 2013-01-01 Epub Date: 2013-05-20 DOI:10.1155/2013/398253
Victor Villar, Jelena Kocic, Juan F Santibanez
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引用次数: 0

Abstract

Purpose. To determine whether Ski-interacting protein (SKIP) regulates TGF- β 1-stimulated expression of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and uPA Inhibitor (PAI-1) in the androgen-independent human prostate cancer cell model. Materials and Methods. PC-3 prostate cancer cell line was used. The role of SKIP was evaluated using synthetic small interference RNA (siRNA) compounds. The expression of uPA, MMP-9, and PAI-1 was evaluated by zymography assays, RT-PCR, and promoter transactivation analysis. Results. In PC-3 cells TGF- β 1 treatment stimulated uPA, PAI-1, and MMP-9 expressions. The knockdown of SKIP in PC-3 cells enhanced the basal level of uPA, and TGF- β 1 treatment inhibited uPA production. Both PAI-1 and MMP-9 production levels were increased in response to TGF- β 1. The ectopic expression of SKIP inhibited both TGF- β 1-induced uPA and MMP-9 promoter transactivation, while PAI-1 promoter response to the factor was unaffected. Conclusions. SKIP regulates the expression of uPA, PAI-1, and MMP-9 stimulated by TGF- β 1 in PC-3 cells. Thus, SKIP is implicated in the regulation of extracellular matrix degradation and can therefore be suggested as a novel therapeutic target in prostate cancer treatment.

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Skip 可调控 TGF- β 1 诱导的人 PC-3 前列腺癌细胞细胞外基质降解蛋白酶的表达。
目的确定 Ski-interacting 蛋白(SKIP)是否调节 TGF- β 1 刺激的尿激酶型纤溶酶原激活剂(uPA)、基质金属蛋白酶-9(MMP-9)和uPA 抑制剂(PAI-1)在雄激素依赖性人类前列腺癌细胞模型中的表达。材料与方法。使用 PC-3 前列腺癌细胞系。使用合成的小干扰 RNA(siRNA)化合物评估 SKIP 的作用。通过酶谱分析、RT-PCR 和启动子转录分析评估 uPA、MMP-9 和 PAI-1 的表达。结果在 PC-3 细胞中,TGF- β 1 处理刺激了 uPA、PAI-1 和 MMP-9 的表达。PC-3 细胞中 SKIP 的敲除提高了 uPA 的基础水平,而 TGF- β 1 处理抑制了 uPA 的产生。PAI-1 和 MMP-9 的生成水平在 TGF- β 1 的作用下均有所增加。异位表达 SKIP 可抑制 TGF- β 1 诱导的 uPA 和 MMP-9 启动子转录,而 PAI-1 启动子对该因子的反应不受影响。结论SKIP 可调节 PC-3 细胞中受 TGF- β 1 刺激的 uPA、PAI-1 和 MMP-9 的表达。因此,SKIP 与细胞外基质降解的调控有关,可作为治疗前列腺癌的新靶点。
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来源期刊
Prostate Cancer
Prostate Cancer ONCOLOGY-
CiteScore
2.70
自引率
0.00%
发文量
9
审稿时长
13 weeks
期刊介绍: Prostate Cancer is a peer-reviewed, Open Access journal that provides a multidisciplinary platform for scientists, surgeons, oncologists and clinicians working on prostate cancer. The journal publishes original research articles, review articles, and clinical studies related to the diagnosis, surgery, radiotherapy, drug discovery and medical management of the disease.
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