Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression.
Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression.
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DOI：
10.1002/pros.21213
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发表时间：
2010-12-01
期刊：
影响因子：
2.8
通讯作者：
Wu, Wen-Shu
中科院分区：
文献类型：
--
作者：
Liu, Jun;Uygur, Berna;Zhang, Zhonghui;Shao, Lijian;Romero, Diana;Vary, Calvin;Ding, Qiang;Wu, Wen-Shu
Slug是Snail/Slug锌指家族的一种转录因子，与肿瘤的转移有关，但其在前列腺癌细胞增殖中的作用尚不清楚。通过Western印迹、RT-PCR和QPCR分析检测SLUG和其他基因的表达水平。SLUG的强制表达是由逆转录病毒和腺病毒介导的。Slug被shRNA下调。用四甲基偶氮唑盐比色法和细胞快速增殖法检测细胞生长情况。在这里，我们证明了Slug在小鼠前列腺癌和人前列腺癌LNCaP、PC-3和22Rv1细胞系中的表达升高。强制表达Slug抑制了前列腺癌PC-3和DU-145细胞的增殖。相反，shRNA降低Slug的表达促进了PC-3癌细胞的生长。与这些数据一致的是，我们发现在前列腺癌细胞中强制表达Slug会导致G1期细胞周期停滞。此外，Slug的异位表达降低了PC-3和DU-145细胞中细胞周期蛋白D1的表达，而shRNA敲除Slug基因上调了这两种癌细胞中细胞周期蛋白D1的表达。此外，我们还证明了细胞周期蛋白D1的异位表达可以缓解Slug对前列腺癌细胞增殖的抑制作用。我们提供了第一个令人信服的证据，证明Slug是前列腺癌细胞增殖的负调节因子。我们在这项研究中的发现不同于先前报道的作为肿瘤转移促进剂的Slug的作用，并提示Slug是一个预后标志物和潜在的治疗靶点。
Slug is a transcription factor of the Snail/Slug zinc-finger family and is implicated in metastasis of tumors, but its role in cell proliferation of prostate cancers is unclear. Expression level of Slug and other genes was examined by Western blot, RT-PCR, and QPCR analyses. The forced expression of Slug was mediated by retroviruses and adenoviruses. Slug was down-regulated by shRNA. Cell growth was measured by the MTT assay and the quick cell proliferation assay. Here, we demonstrated that Slug expression is elevated in mouse prostate tumors, and human prostate cancer cell lines LNCaP, PC-3, and 22RV1. Forced expression of Slug inhibited proliferation of prostate cancer cells PC-3 and DU-145. Conversely, reduced expression of Slug by shRNA promoted growth of PC-3 cancer cells. Consistent with these data, we found that forced expression of Slug in prostate cancer cells led to G1 cell cycle arrest. Furthermore, ectopic expression of Slug decreased cyclin D1 expression in both PC-3 and DU-145 cells, and knockdown of Slug by shRNA upregulated cyclin D1 expression in these cancer cells. In addition, we demonstrated that ectopic expression of cyclin D1 relieved Slug-mediated inhibition of proliferation of prostate cancer cells. We provide the first compelling evidence that Slug is a negative regulator of proliferation of prostate cancer cells. Our findings in this study are distinct from the previously reported role of Slug as a promoter for tumor metastasis, and suggest that Slug is a prognostic marker and potential therapeutic target.
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影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
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