The role of zinc transporter ZIP4 in prostate carcinoma
The role of zinc transporter ZIP4 in prostate carcinoma
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DOI：
10.1016/j.urolonc.2010.11.010
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发表时间：
2012-11-01
影响因子：
2.7
通讯作者：
Kong, Chui-ze
中科院分区：
文献类型：
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作者：
Chen, Qi-guang;Zhang, Zhe;Kong, Chui-ze
目的：正常前列腺组织具有积累高水平锌的独特功能。这种能力在前列腺恶性肿瘤发展的早期阶段就丧失了。 ZIP4 是一种重要的锌转运蛋白。在本研究中，我们探讨了ZIP4在前列腺癌中的表达，并探讨了ZIP4在体外对癌症生长的功能贡献。方法：通过实时RT-PCR和蛋白质印迹法检测14例前列腺癌和20例BPH组织中ZIP4的表达。为了研究ZIP4在前列腺癌细胞中的生物学功能，在前列腺癌细胞系DU145（DU145-ZIP4）中建立了ZIP4在细胞中的稳定过表达，并在前列腺癌细胞系22RVI（22RVI-shRNA）中建立了ZIP4短发夹RNA（shRNA）在细胞中的稳定表达。检测前列腺癌细胞的增殖、迁移和侵袭能力。结果：与BPH组织相比，前列腺癌组织中ZIP4 mRNA和蛋白的表达显着下调。然而，我们发现ZIP4表达与前列腺癌的病理分级之间没有相关性。在体外研究中，ZIP4的过表达不仅抑制前列腺癌细胞株DU145-ZIP4的增殖，而且抑制其侵袭能力。同时，我们发现ZIP4的沉默与22RVI-shRNA细胞系中细胞增殖和侵袭能力的增加相关。然而，与对照相比，DU145-ZIP4和22RVI-shRNA细胞均表现出细胞迁移能力显着降低。结论：结果表明ZIP4表达在前列腺癌中下调，它可能作为前列腺癌的有前途的生物标志物。 ZIP4对前列腺癌细胞的增殖和侵袭具有抑制作用。这表明ZIP4可能是一种抑癌基因，ZIP4的下调可能是前列腺癌发展的关键早期事件。 (C) 2012 Elsevier Inc. 保留所有权利。
Objective: Normal prostate tissues have a unique function of accumulating high levels of zinc. This capability is lost during the early stage in the development of prostate malignancy. ZIP4 is an important zinc transporter. In this study, we explore the expression of ZIP4 in prostate carcinoma and invest the functional contributions of ZIP4 to cancer growth in vitro.Methods: ZIP4 expression was detected in 14 prostate carcinoma and 20 BPH tissues by real-time RT-PCR and western blot. To invest the biological function of ZIP4 in prostate carcinoma cells, ZIP4 stable over-expression in cells was established in prostate carcinoma cell line DU145 (DU145-ZIP4) and ZIP4 short hairpin RNA(shRNA) expression in stable cells was also established in prostate carcinoma cell line 22RVI (22RVI-shRNA). The proliferation, migration, and invasion ability of the prostate carcinoma cells were detected.Results: The expression of ZIP4 mRNA and protein are significantly down-regulated in prostate carcinoma tissues compared with that in BPH tissues. However, we found that there was no correlation between the ZIP4 expression and the pathologic grade of prostate carcinoma. In in vitro studies, over-expression of ZIP4 not only inhibits the proliferation but also inhibits the invasive ability of prostate carcinoma cell line DU145-ZIP4. At the same time, we found silencing of ZIP4 was associated with increased cell proliferation and invasion ability in 22RVI-shRNA cell line. However, both DU145-ZIP4 and 22RVI-shRNA cells showed a significant reduction on cell migration ability compared with the control.Conclusion: The results indicate that ZIP4 expression is down-regulated in prostate carcinoma and it may serve as a promising biomarker for prostate carcinoma. ZIP4 has an inhibitory effect on prostate carcinoma cell proliferation and invasion. It suggests that ZIP4 may be a tumor suppressor gene and down-regulation of ZIP4 may be a critical early event in the development of prostate carcinoma. (C) 2012 Elsevier Inc. All rights reserved.