Differential zinc accumulation and expression of human zinc transporter 1 (hZIP1) in prostate glands
Differential zinc accumulation and expression of human zinc transporter 1 (hZIP1) in prostate glands
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DOI：
10.1016/j.ymeth.2010.08.004
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Bagasra, Omar
中科院分区：
文献类型：
--
作者：
Johnson, Leslie A.;Kanak, Mazhar A.;Bagasra, Omar
锌是许多细胞功能所必需的，但也有潜在的毒性。因此，锌的动态平衡是由分布在不同细胞和亚细胞中的各种转运蛋白和其他蛋白质来动态维持的。锌的转运由两个主要的蛋白质家族来调节：Zip家族，它介导了锌的内流；以及锌纳米管，它主要与锌在细胞内的固存有关，从而参与了降低细胞质中锌的游离离子浓度。在前列腺上皮细胞中，高细胞锌的积累是一种特殊的功能，是这些细胞执行产生和分泌前列腺液的主要生理功能所必需的。锌蓄积丧失是前列腺癌最一致、最持久的特征。目前，还没有直接的方法来测定不同类型的前列腺细胞(间质、腺上皮、腺泡和肌肉)中的相对锌水平，也没有可靠的方法来比较腺体中正常和恶性区域的锌含量。在这里，我们报告了一种新的方法来显示差异锌染色方法，该方法与前列腺癌发展的不同阶段相关，并通过原位逆转录-聚合酶链式反应杂交(ISRTPCR)显示与前列腺癌不同发展阶段相关的人锌转运蛋白1-hZIP1的原位表达，该方法与差异锌染色方法测定的相对锌水平相关。利用这些方法，我们首次发现：(1)在恶性腺体中锌的相对水平很低或缺失；(2)正常腺体中的锌水平在腺上皮和间质组织中都很高；(3)在癌前病变的腺体中锌水平开始下降，并先于肿瘤的发生发展；(4)人类锌转运蛋白1(HZIP1)的表达似乎与前列腺癌中的锌水平有关，可能是该器官中主要的锌调节因子。(C)2010 Elsevier Inc.保留所有权利。
Zinc (Zn) is essential for a very large number and variety of cellular functions but is also potentially toxic. Zn homeostasis is therefore dynamically maintained by a variety of transporters and other proteins distributed in distinct cellular and subcellular compartments. Zn transport is mediated by two major protein families: the Zip family, which mediates Zn influx, and the ZnTs which are primarily linked to Zn sequestration into intracellular compartments and are, thereby, involved in lowering cytoplasmic Zn free ion concentrations. In the prostate epithelial cell, the accumulation of high cellular zinc is a specialized function that is necessary for these cells to carry out the major physiological functions of production and secretion of prostatic fluids. The loss of Zn accumulation is the most consistent and persistent characteristic of prostate malignancy. Currently, there are no direct methods to determine the relative Zn levels in various cell types of prostate gland (i.e. stroma, glandular epithelia, acini, and muscular) and no reliable ways to compare the Zn in normal versus malignant areas of the gland. Here we report a new method to show a differential Zn staining method that correlates with various stages of prostate cancer development in situ and expression of a human Zn transporter1-hZIP1 - in situ by in situ reverse transcriptase-polymerase chain reaction hybridization (ISRTPCR) that correlate with the relative Zn levels determined by the differential Zn staining method. By utilizing these methods, we show for the first time that: (1) the relative Zn levels are very low to absent in the malignant glands, (2) normal glands show high Zn levels in both glandular epithelia as well as in stromal tissues, (3) the Zn levels begin to decrease in pre-malignant glands and precedes the development of malignancy, and (4) the expression of human Zn transporter1 (hZIP1) appears to correlate with the Zn levels in the prostate glands and may be the major Zn regulator in this organ. (C) 2010 Elsevier Inc. All rights reserved.