ZIP14 Zinc Transporter Downregulation and Zinc Dep

Authors: Renty B Franklin Bernard A Levy Jing Zou Nader Hanna Mohamed Mokhtar Desouki Omar Bagasra Leslie A Johnson Leslie C Costello

Publish Date: 2011/03/05

Volume: 43, Issue: 2, Pages: 249-257

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Abstract

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 zincIntracellular 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 growthZIP14 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 carcinogenesisWe are grateful to Dr Robert Cousins University of Florida for kindly providing us with the ZIP14 antibody employed in this study We are also grateful to Dr Peter Zalewski University of Adelaide Australia for kindly providing us with the Zinquin ester employed in this study These studies were supported by NIH grants DK076783 and CA79903

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