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hZIP1 zinc transporter down‐regulation in prostate cancer involves the overexpression of ras responsive element binding protein‐1 (RREB‐1)
Author(s) -
Zou Jing,
Milon Beatrice C.,
Desouki Mohamed M.,
Costello Leslie C.,
Franklin Renty B.
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21368
Subject(s) - prostate cancer , prostate , tissue microarray , carcinogenesis , immunohistochemistry , biology , cancer research , endocrinology , pathology , cancer , medicine , immunology , genetics
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. Prostate 71:1518–1524, 2011. © 2011 Wiley‐Liss, Inc.