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饮食锌补充剂对乳腺癌中锌转运蛋白的调节作用

Regulation of zinc transporters by dietary zinc supplement in breast cancer.

作者信息

Sun Daoxu, Zhang Lianying, Wang Yongsheng, Wang Xiaolei, Hu Xiaoyan, Cui Fu-Ai, Kong Feng

机构信息

Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China.

出版信息

Mol Biol Rep. 2007 Dec;34(4):241-7. doi: 10.1007/s11033-007-9082-6. Epub 2007 May 1.

DOI:10.1007/s11033-007-9082-6
PMID:17473989
Abstract

Zinc is essential for cell growth and is a co-factor for more than 300 enzymes, representing over 50 different enzyme classes. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while ZIP transporters increase intracellular zinc. Previous studies have shown that zinc concentration in breast cancer tissues is higher than that in normal breast tissues. However, the mechanisms involved and the relations to zinc transporters are still unknown. A series of zinc transporters are characterized in this article and several of that are emphasized in view of their unique tissue-specific expressions. Established human breast cancer in a nude mice model is used. With a dietary zinc supplement treatment, ZnT-1 mRNA expression in established human breast cancer is raised by 24%, and is nearly 2 times of that in basal diet. ZIP1, ZIP2 and LIV-1 mRNA are the same between two treatment groups. Moreover, no significant changes of these zinc transporters expressions are found between differential breast cancer cell lines in the nude mice model. This is the first report, which detects the zinc transporters expressions in established human breast cancer in nude mice model. These results lead to the constitutive expression and response to zinc in different tissues. In addition to that, ZnT-1 seems to have played an important role in zinc homeostasis, even in breast cancer.

摘要

锌对于细胞生长至关重要,并且是300多种酶的辅助因子,这些酶分属于50多种不同的酶类。已鉴定出两个与锌稳态相关的基因家族。锌转运体(ZnT)会降低细胞内锌含量,而锌铁转运蛋白(ZIP)则会增加细胞内锌含量。先前的研究表明,乳腺癌组织中的锌浓度高于正常乳腺组织。然而,其中涉及的机制以及与锌转运体的关系仍不清楚。本文对一系列锌转运体进行了表征,并鉴于它们独特的组织特异性表达而着重强调了其中几种。使用裸鼠模型中的人源化乳腺癌。通过膳食锌补充剂处理,人源化乳腺癌中锌转运体-1(ZnT-1)的mRNA表达提高了24%,几乎是基础饮食组的2倍。两个处理组之间锌铁转运蛋白1(ZIP1)、锌铁转运蛋白2(ZIP2)和肝脏-intestine-维生素转运蛋白1(LIV-1)的mRNA表达相同。此外,在裸鼠模型的不同乳腺癌细胞系之间,未发现这些锌转运体的表达有显著变化。这是首篇在裸鼠模型中检测人源化乳腺癌中锌转运体表达的报告。这些结果导致了锌在不同组织中的组成性表达和反应。除此之外,锌转运体-1似乎在锌稳态中发挥了重要作用,即使在乳腺癌中也是如此。

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Zip3 (Slc39a3) functions in zinc reuptake from the alveolar lumen in lactating mammary gland.

本文引用的文献

1
hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer.hZIP1锌摄取转运体下调与前列腺癌中的锌耗竭
Mol Cancer. 2005 Sep 9;4:32. doi: 10.1186/1476-4598-4-32.
2
Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.假定的锌转运蛋白LIV-1的表达水平与乳腺癌患者较好的预后相关。
Int J Cancer. 2005 Dec 20;117(6):961-73. doi: 10.1002/ijc.21235.
3
Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.
Zip3(溶质载体家族39成员3)在哺乳期乳腺的肺泡腔锌再摄取过程中发挥作用。
Am J Physiol Regul Integr Comp Physiol. 2009 Jul;297(1):R194-201. doi: 10.1152/ajpregu.00162.2009. Epub 2009 May 20.
4
Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7.人乳腺癌细胞MCF-7中LIV-1与E-钙黏蛋白表达的一致性相关性
Mol Biol Rep. 2009 Apr;36(4):653-9. doi: 10.1007/s11033-008-9225-4. Epub 2008 Mar 11.
通过膳食补充锌对人小肠中锌转运体的稳态调节。
Gut. 2005 Apr;54(4):469-78. doi: 10.1136/gut.2004.041962.
4
Mammalian zinc transporters.哺乳动物锌转运蛋白。
Annu Rev Nutr. 2004;24:151-72. doi: 10.1146/annurev.nutr.24.012003.132402.
5
Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer.锌转运蛋白LIVI控制斑马鱼原肠胚组织者中的上皮-间质转化。
Nature. 2004 May 20;429(6989):298-302. doi: 10.1038/nature02545. Epub 2004 May 5.
6
Differential expression of hZnT-4 in human prostate tissues.hZnT-4在人前列腺组织中的差异表达。
Prostate. 2004 Mar 1;58(4):374-81. doi: 10.1002/pros.10344.
7
Overview of mammalian zinc transporters.哺乳动物锌转运蛋白概述。
Cell Mol Life Sci. 2004 Jan;61(1):49-68. doi: 10.1007/s00018-003-3148-y.
8
Structure, function, and regulation of a subfamily of mouse zinc transporter genes.小鼠锌转运蛋白基因一个亚家族的结构、功能及调控
J Biol Chem. 2003 Dec 12;278(50):50142-50. doi: 10.1074/jbc.M304163200. Epub 2003 Oct 2.
9
Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells.人类 ZIP1 是一种主要的锌摄取转运蛋白,用于锌在前列腺细胞中的积累。
J Inorg Biochem. 2003 Aug 1;96(2-3):435-42. doi: 10.1016/s0162-0134(03)00249-6.
10
Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters.LIV-1的结构-功能分析,LIV-1是一种与乳腺癌相关的蛋白质,属于锌转运体新亚家族。
Biochem J. 2003 Oct 1;375(Pt 1):51-9. doi: 10.1042/BJ20030478.