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Prostate. 2011 Oct 1;71(14):1518-24. doi: 10.1002/pros.21368. Epub 2011 Feb 25.

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

Author information

1
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland Baltimore, Baltimore, Maryland.

Abstract

BACKGROUND:

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.

METHODS:

Overexpression 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 (TMAs) and tissue sections was used to determine the levels of RREB-1 expression in prostate in situ.

RESULTS:

Overexpression 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.

CONCLUSIONS:

RREB-1 overexpression 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.

KEYWORDS:

RREB-1; hZIP1; prostate cancer; zinc transporter

PMID:
21360563
PMCID:
PMC3116060
DOI:
10.1002/pros.21368
[Indexed for MEDLINE]
Free PMC Article
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