ERK5 regulates invasiveness of osteosarcoma by inducing MMP-9
ERK5 regulates invasiveness of osteosarcoma by inducing MMP-9
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DOI：
10.1002/jor.22025
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发表时间：
2012-07-01
影响因子：
2.8
通讯作者：
Seo, Sung Wook
中科院分区：
文献类型：
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作者：
Kim, Sang-Min;Lee, Hyewon;Seo, Sung Wook
本研究旨在探讨ERK 5在骨肉瘤细胞侵袭中的作用。本研究使用人OS细胞系（MG 63、SaOS和U2 OS）和原代OS细胞。Western blot和RT-PCR检测ERK 5和MMP-9的表达。为了评估ERK 5的生物学作用，在使用siRNA沉默ERK 5后进行增殖测定（MTT）和侵袭测定（BD Matrigel（TM））。采用RT-PCR和酶谱分析沉默ERK 5后MMPs的表达。ERK 5在U2 OS和原代OS细胞中明显过表达。RT-PCR结果显示，MG 63和SaOS均不表达MMP-9。ERK 5沉默不抑制OS细胞的增殖。然而，ERK 5沉默显著减少了侵袭试验中的侵袭细胞数量。ERK 5沉默后MMP-9的表达特异性降低。酶谱分析显示，ERK 5抑制后MMP-9的酶活性也降低。ERK 5的表达通过诱导MMP-9的表达来调节OS细胞的侵袭。因此，ERK 5可能是MMP-9表达的侵袭性OS的一个新的治疗靶点。(C)2011骨科研究学会。由威利期刊公司出版J Orthop Res 30：10401044，2012
The purpose of this study is to determine the role of ERK5 in cellular invasion of osteosarcoma (OS). The human OS cell line (MG63, SaOS, and U2OS) and primary OS cells were used for the study. The expression of ERK5 and MMP-9 in each cell was examined by western blot or RT-PCR. To evaluate the biological role of ERK5, proliferation assay (MTT) and invasion assay (BD Matrigel (TM)) were performed after silencing ERK5 using siRNA. MMPs expressions were analyzed using RT-PCR and zymography after silencing ERK5. ERK5 was distinctly overexpressed in U2OS and primary OS cell. Both of them also expressed MMP-9, which was not shown in MG63 and SaOS in RT-PCR. ERK5 silencing did not suppress the proliferation of OS cells. However, ERK5 silencing significantly reduced the number of invading cells in invasion assay. The expression of MMP-9 was specifically reduced after silencing ERK5. The zymography showed that the enzyme activity of MMP-9 was also reduced after ERK5 suppression. The expression of ERK5 regulates the invasion of OS cells by inducing MMP-9 expression. Therefore, ERK5 may be a new therapeutic target in invasive OS expressing MMP-9. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:10401044, 2012