First Affiliated Hospital of China Medical University, Shenyang, China.
Urol Oncol. 2012 Nov-Dec;30(6):906-11. doi: 10.1016/j.urolonc.2010.11.010. Epub 2011 Jul 30.
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.
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 22RV1(22RV1-shRNA). The proliferation, migration, and invasion ability of the prostate carcinoma cells were detected.
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 22RV1-shRNA cell line. However, both DU145-ZIP4 and 22RV1-shRNA cells showed a significant reduction on cell migration ability compared with the control.
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.
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丧失。ZIP4 是一种重要的锌转运蛋白。在这项研究中，我们探索了 ZIP4 在前列腺癌中的表达，并研究了 ZIP4 在体外对癌症生长的功能贡献。
通过实时 RT-PCR 和 Western blot 检测 14 例前列腺癌和 20 例 BPH 组织中的 ZIP4 表达。为了研究 ZIP4 在前列腺癌细胞中的生物学功能，我们在前列腺癌细胞系 DU145（DU145-ZIP4）中建立了 ZIP4 的稳定过表达，并且在前列腺癌细胞系 22RV1（22RV1-shRNA）中也建立了 ZIP4 的短发夹 RNA（shRNA）表达。检测前列腺癌细胞的增殖、迁移和侵袭能力。
与 BPH 组织相比，前列腺癌组织中 ZIP4 mRNA 和蛋白的表达明显下调。然而，我们发现 ZIP4 的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，过表达 ZIP4 不仅抑制了前列腺癌细胞系 DU145-ZIP4 的增殖，而且抑制了其侵袭能力。同时，我们发现 ZIP4 的沉默与 22RV1-shRNA 细胞系中细胞增殖和侵袭能力的增加有关。然而，与对照组相比，DU145-ZIP4 和 22RV1-shRNA 细胞的迁移能力均显著降低。
结果表明，ZIP4 在前列腺癌中表达下调，可能作为前列腺癌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 可能是一种肿瘤抑制基因，ZIP4 的下调可能是前列腺癌发展的早期关键事件。
