Back to Search Start Over

Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats.

Authors :
Ruiyan Jing
Zi-Xuan Wang
Farber, John L.
Fong, Louise Y.
Smalley, Karl J.
Hongping Chen
Taccioli, Cristian
Sili Fan
Fiehn, Oliver
Hansjuerg Alder
Kay Huebner
Croce, Carlo M.
Source :
Proceedings of the National Academy of Sciences of the United States of America; 11/20/2018, Vol. 115 Issue 47, pE11091-E11100, 10p
Publication Year :
2018

Abstract

Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR- 183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zndepleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold downregulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
115
Issue :
47
Database :
Complementary Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
133159063
Full Text :
https://doi.org/10.1073/pnas.1813956115