hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).

hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).
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DOI:
10.1002/pros.21368
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发表时间:
2011-10-01
期刊:
影响因子:
2.8
通讯作者:
Franklin, Renty B.
Franklin, Renty B.
中科院分区:
医学3区
文献类型:
--
作者:
Zou, Jing;Milon, Beatrice C.;Desouki, Mohamed M.;Costello, Leslie C.;Franklin, Renty B.

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锌水平的显著降低是前列腺癌的一贯特征;这是ZIP 1锌转运蛋白下调的结果。本研究的目的是确定RREB-1转录是否参与ZIP 1基因表达的下调,并确定RREB-1在良性和恶性前列腺原位表达。使用RREB-1的过表达和siRNA敲低来确定RREB-1对PC-3细胞中hZIP 1丰度的影响。采用组织芯片(TMA)和组织切片的免疫组化方法原位测定前列腺中RREB-1的表达水平。RREB-1的过表达导致PC-3细胞质膜中hZIP 1丰度的降低;而siRNA敲低显著增加hZIP 1表达。前列腺TMA和组织切片显示RREB-1和hZIP 1染色之间的反比关系。RREB-1过表达导致hZIP 1的下调,并导致前列腺癌中hZIP 1表达和锌的丧失。这是前列腺癌发生的早期事件。
A marked decrease in the level of zinc is a consistent characteristic of prostate cancer; which results from down regulation of ZIP1 zinc transporter. The aim of this study was to determine if RREB-1 transcription is involved in the down regulation of ZIP1 gene expression; and to determine the expression of RREB-1 in benign and cancerous prostate in situ. Over expression and siRNA knock down of RREB-1 were used to determine the effect of RREB-1 on hZIP1 abundance in PC-3 cells. Immunohistochemistry with tissue microarrays (TMA) and tissue sections was used to determine the levels of RREB-1 expression in prostate in situ. Over expression of RREB-1 resulted in a decrease in the abundance of hZIP1 in the plasma membrane of PC-3 cells; whereas siRNA knock down significantly increased hZIP1 expression. Prostate TMAs and tissue sections showed an inverse relationship between RREB-1 and hZIP1 staining. RREB-1 over expression results in down regulation of hZIP1 and contributes to the loss of hZIP1 expression and zinc in prostate cancer. This is an early event in prostate carcinogenesis.
DOI: 10.1186/1476-4598-5-17
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期刊: MOLECULAR CANCER
影响因子: 37.3
作者:
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通讯作者: Franklin, Renty B
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