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

Autor:	Fong LY; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107; louise.fong@jefferson.edu carlo.croce@osumc.edu.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107., Jing R; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107., Smalley KJ; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107., Wang ZX; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107., Taccioli C; Department of Animal Medicine, Health and Production, University of Padova, 35122 Padova PD, Italy., Fan S; National Institutes of Health West Coast Metabolomics Center, University of California Davis Genome Center, University of California, Davis, CA 95616., Chen H; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107., Alder H; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210.; The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210., Huebner K; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210.; The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210., Farber JL; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107., Fiehn O; National Institutes of Health West Coast Metabolomics Center, University of California Davis Genome Center, University of California, Davis, CA 95616.; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, 21589 Jeddah, Saudi Arabia., Croce CM; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210; louise.fong@jefferson.edu carlo.croce@osumc.edu.; The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Nov 20; Vol. 115 (47), pp. E11091-E11100. Date of Electronic Publication: 2018 Nov 05.
DOI:	10.1073/pnas.1813956115
Abstrakt:	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 Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation 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. Competing Interests: The authors declare no conflict of interest. (Copyright © 2018 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu