ZIP14 zinc transporter downregulation and zinc depletion in the development and progression of hepatocellular cancer.
ZIP14 zinc transporter downregulation and zinc depletion in the development and progression of hepatocellular cancer.
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DOI：
10.1007/s12029-011-9269-x
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发表时间：
2012-06
影响因子：
1.6
通讯作者：
Costello, Leslie C
中科院分区：
文献类型：
--
作者：
Franklin, Renty B;Levy, Bernard A;Zou, Jing;Hanna, Nader;Desouki, Mohamed Mokhtar;Bagasra, Omar;Johnson, Leslie A;Costello, Leslie C
肝细胞癌（HCC）是美国和世界范围内一种致命且增长最快的癌症。 HCC 的病因和发展因素仍然很大程度上未知。肝癌中锌含量显着减少。它在 HCC 中的作用和参与尚未确定。我们研究了细胞锌变化与恶性肿瘤发展的关系，并鉴定了与肝癌细胞无法积累锌相关的潜在锌转运蛋白。在正常和肝癌组织切片上原位检测正常肝细胞与肝癌细胞中的相对锌水平。通过免疫组织化学鉴定 ZIP1、2、3 和 14 转运蛋白。在早期和晚期恶性肿瘤中，与正常肝细胞相比，HCC 肝癌细胞的细胞内锌水平显着降低。 ZIP14 转运蛋白位于正常肝细胞的质膜上，表明其具有吸收和积累锌的功能。肝癌细胞中缺乏转运蛋白，其基因表达下调。 ZIP14 的变化与锌的减少同时发生。 ZIP1、2、3 与正常肝细胞摄取锌和 HCC 锌消耗无关。 HepG2 细胞表现出 ZIP14 转运蛋白。锌处理会抑制它们的生长。 ZIP14 下调可能与 HCC 肝癌细胞中锌的消耗有关。这些事件发生在恶性肿瘤发展的早期，可能是为了保护恶性细胞免受锌的肿瘤抑制作用。这为与 HCC 致癌相关的重要因素提供了新的见解。
Hepatocellular cancer (HCC) is a deadly and most rapidly increasing cancer in the USA and worldwide. The etiology and factors involved in development of HCC remain largely unknown. A marked decrease in zinc occurs in HCC. Its role and involvement in HCC has not been identified. We investigated the relationship of cellular zinc changes to the development of malignancy, and the identification of potential zinc transporters associated with the inability of hepatoma cells to accumulate zinc. The detection of relative zinc levels in situ in normal hepatic cells vs. hepatoma was performed on normal and HCC tissue sections. ZIP1, 2, 3, and 14 transporters were identified by immunohistochemistry. Intracellular zinc levels are markedly decreased in HCC hepatoma cells vs. normal hepatic cells in early stage and advanced stage malignancy. ZIP14 transporter is localized at the plasma membrane in normal hepatocytes, demonstrating its functioning for uptake and accumulation of zinc. The transporter is absent in the hepatoma cells and its gene expression is downregulated. The change in ZIP14 is concurrent with the decrease in zinc. ZIP1, 2, 3 are not associated with normal hepatocyte uptake of zinc, and HCC zinc depletion. HepG2 cells exhibit ZIP14 transporter. Zinc treatment inhibits their growth. ZIP14 downregulation is likely involved in the depletion of zinc in the hepatoma cells in HCC. These events occur early in the development of malignancy possibly to protect the malignant cells from tumor suppressor effects of zinc. This provides new insight into important factors associated with HCC carcinogenesis.