Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration.
Zip4 (Slc39a4) expression is activated in hepatocellular carcinomas and functions to repress apoptosis, enhance cell cycle and increase migration.
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DOI：
10.1371/journal.pone.0013158
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发表时间：
2010-10-04
期刊：
影响因子：
3.7
通讯作者：
Andrews, Glen K
中科院分区：
文献类型：
--
作者：
Weaver, Benjamin P;Zhang, Yuxia;Andrews, Glen K
背景：锌转运蛋白ZIP 4（Slc 39 a4）对哺乳动物的正常发育非常重要，是小鼠的必需基因。最近的研究表明，这个基因也可能发挥作用，在胰腺cancer.METHODS/PRINCIPAL FINDINGS：在此，我们提出的证据表明，这是必不可少的锌转运蛋白在肝细胞癌中表达。Zip 4 mRNA和蛋白质显着升高，在大多数人肝细胞癌的肝细胞相对于非癌周围组织，以及发生在法尼醇X受体敲除小鼠肝细胞癌的肝细胞。有趣的是，Geo和Oncomine数据库中微阵列数据的荟萃分析表明，Zip 4 mRNA也可能在许多类型的癌症中升高。在培养的细胞系中检查ZIP 4的潜在作用机制。RNAi敲除小鼠Hepa细胞中的Zip 4显著增加了细胞凋亡，并且当细胞从羟基脲阻断释放到缺锌培养基中时，适度减缓了从G（0）/G（1）到S期的进展。细胞迁移实验表明，RNA干扰敲低Zip 4在Hepa细胞抑制体外migration，而被迫过度表达Hepa细胞和MCF-7细胞增强体外migration.CONCLUSIONS：ZIP 4可能发挥作用，在收购锌的肝细胞癌，并可能有许多不同的癌细胞类型，导致抑制凋亡，提高生长速度和增强侵袭行为。
BACKGROUND: The zinc transporter ZIP4 (Slc39a4) is important for proper mammalian development and is an essential gene in mice. Recent studies suggest that this gene may also play a role in pancreatic cancer.METHODS/PRINCIPAL FINDINGS: Herein, we present evidence that this essential zinc transporter is expressed in hepatocellular carcinomas. Zip4 mRNA and protein were dramatically elevated in hepatocytes in the majority of human hepatocellular carcinomas relative to noncancerous surrounding tissues, as well as in hepatocytes in hepatocellular carcinomas occurring in farnesoid X receptor-knockout mice. Interestingly, meta-analysis of microarray data in the Geo and Oncomine databases suggests that Zip4 mRNA may also be elevated in many types of cancer. Potential mechanisms of action of ZIP4 were examined in cultured cell lines. RNAi knockdown of Zip4 in mouse Hepa cells significantly increased apoptosis and modestly slowed progression from G(0)/G(1) to S phase when cells were released from hydroxyurea block into zinc-deficient medium. Cell migration assays revealed that RNAi knockdown of Zip4 in Hepa cells depressed in vitro migration whereas forced over-expression in Hepa cells and MCF-7 cells enhanced in vitro migration.CONCLUSIONS: ZIP4 may play a role in the acquisition of zinc by hepatocellular carcinomas, and potentially many different cancerous cell-types, leading to repressed apoptosis, enhanced growth rate and enhanced invasive behavior.