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United States Department of Agriculture

Agricultural Research Service

Research Project: Linking Foods, Behavior and Metabolism to Promote a Healthy Body Weight

Location: Obesity and Metabolism Research Unit

Title: A null-mutation in the Znt7 gene accelerates prostate tumor formation in a transgenic adenocarcinoma mouse prostate model

Authors
item Tepaamorndech, Surapun -
item Huang, Liping
item Kirschke, Catherine

Submitted to: Cancer Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 14, 2011
Publication Date: May 28, 2011
Repository URL: http://www.sciencedirect.com/science/article/pii/S0304383511002229
Citation: Tepaamorndech, S., Huang, L., Kirschke, C.P. 2011. A null-mutation in the Znt7 gene accelerates prostate tumor formation in a transgenic adenocarcinoma mouse prostate model. Cancer Letters. 308 (2011) 33-42.

Interpretive Summary: The prostate is a gland of the male reproductive system. The main function of the prostate is to store and secrete a clear fluid that helps prolong the lifespan of sperms. Decrease of zinc in the fluid secreting cells (epithelial cells) of human prostate has been implicated in the development of prostate cancer. To investigate the possibility that a decrease in zinc accumulation in the prostate epithelial cells has a role in prostate cancer development, we have generated and characterized a transgenic adenocarcinoma mouse prostate (TRAMP) model with a Znt7-null genetic background. Four-week-old male TRAMP mice (TRAMP/Znt7+/+ and TRAMP/Znt7-/-) were fed a semi-purified diet containing 15 mg Zn/kg diet for 2-24 weeks. Mice were euthanized at 6, 8, 16, and 24 weeks old. At 16 weeks of age, 25% TRAMP/Znt7-/- mice developed prostate tumors and two-third of mice with prostate tumors had tumor metastasized to the adjacent lymph nodes while no prostate tumor was detected in the control TRAMP mice. By 28 weeks, 67% TRAMP/Znt7-/- mice developed prostate tumors while only 22% control TRAMP mice developed prostate tumors. Furthermore, apoptosis (programmed cell death) was significantly reduced in the prostate of TRAMP/Znt7-/- mice. In conclusion, a null mutation of Znt7 gene promotes prostate cancer development in TRAMP mice.

Technical Abstract: Decrease of cellular zinc in the epithelium of the prostate has been implicated in the development of prostate cancer. To investigate whether ZnT7, a zinc transporter involved in intracellular zinc accumulation, plays a role in prostate cancer development, we have generated and characterized a transgenic adenocarcinoma mouse prostate (TRAMP) model with a Znt7-null genetic background. Four-week-old male TRAMP mice (TRAMP/Znt7+/+ and TRAMP/Znt7-/-) were fed a semi-purified diet containing 15 mg Zn/kg diet for 2-24 weeks. Mice were euthanized at 6, 8, 16, and 24 weeks for histopathological analysis of the prostates and for the presence of prostate tumors and lymph node metastasis. At 16 weeks of age, 25% TRAMP/Znt7-/- mice developed prostate tumors and two-third of mice with prostate tumors had tumor metastasized to the draining lymph nodes while no prostate tumor was detected in the control TRAMP mice. By 28 weeks, 67% TRAMP/Znt7-/- mice developed prostate tumors while only 22% control TRAMP mice developed prostate tumors. Furthermore, apoptosis was significantly reduced in the prostate of TRAMP/Znt7-/- mice. In conclusion, a null mutation of Znt7 gene promotes prostate cancer development in TRAMP mice.

Last Modified: 8/21/2014
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