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Authors: Leslie C. Costello, Renty B. Franklin, Jing Zou, Pei Feng, Robert Bok, Mark G. Swanson and John Kurhanewicz

Leslie C. Costello

Corresponding author: lcostello@umaryland.edu
Department of Oncology and Diagnostic Sciences; Dental School and Greenebaum Cancer Center; University of Maryland; Baltimore, MD USA

Renty B. Franklin

Department of Oncology and Diagnostic Sciences; Dental School and Greenebaum Cancer Center; University of Maryland; Baltimore, MD USA

Jing Zou

Department of Oncology and Diagnostic Sciences; Dental School; University of Maryland; Baltimore, MD USA

Pei Feng

Department of Oncology and Diagnostic Sciences; Dental School; University of Maryland; Baltimore, MD USA

Robert Bok

Department of Radiology and Biomedical Imaging; University of California San Francisco; San Francisco, CA USA

Mark G. Swanson

Department of Radiology and Biomedical Imaging; University of California San Francisco; San Francisco, CA USA

John Kurhanewicz

Department of Radiology and Biomedical Imaging; University of California San Francisco; San Francisco, CA USA

Abstract:
Prostate cancer is the second leading cause of cancer deaths among men. The availability of animal models that represent the events and factors that exist in the natural history and biology of human prostate cancer is essential in dealing with prostate cancer. In recent decades and presently, emphasis has been directed at the development and employment of prostate cancer induced in transgenic mice. However, the important consistent hallmark characteristic and event of decrease in zinc and citrate and downregulation of ZIP1 zinc transporter in prostate malignancy has not been studied or identified in any animal model. We investigated the status of these parameters in TRAMP tumors as compared with human prostate cancer. The results show that citrate levels are markedly decreased in the developing and advancing stages of malignancy in TRAMP. Zinc levels are also decreased and ZIP1 transporter is lost in TRAMP tumors. In vitro studies show that zinc treatment of TRAMP C2 cells exhibits cytotoxic effects. Collectively, these results mimic the ZIP1, zinc, and citrate status and relationship that exist in human prostate cancer. This is the first report that establishes the existence of the human prostate zinc/citrate hallmark characteristic and relationship in an animal model. It now appears that the TRAMP model will be suitable for studies relating to the implications and role of zinc- and citrate-related metabolism in the development and progression of human prostate cancer.

Received: September 3, 2011; Accepted: October 11, 2011; Published Online: December 15, 2011

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