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

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.

• Authors: Jing Zou, Beatrice C Milon, Mohamed M Desouki, Leslie C Costello, Renty B Franklin
• Journal: The Prostate (Prostate) Vol. 71 Issue 14 Pg. 1518-24 (Oct 01 2011) ISSN: 1097-0045 [Electronic] United States
• PMID: 21360563 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Cation Transport Proteins
• DNA-Binding Proteins
• RNA, Small Interfering
• RREB1 protein, human
• SLC39A1 protein, human
• Transcription Factors
• Zinc

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Adult
• Aged
• Biopsy
• Cation Transport Proteins (genetics, metabolism)
• Cell Line, Tumor
• DNA-Binding Proteins (genetics, metabolism)
• Down-Regulation (physiology)
• Epigenesis, Genetic (physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Prostatic Neoplasms (genetics, metabolism, pathology)
• RNA, Small Interfering (genetics)
• Transcription Factors (genetics, metabolism)
• Zinc (metabolism)