title: A null-mutation in the Znt7 gene accelerates prostate tumor formation in a transgenic adenocarcinoma mouse prostate model.
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, played a role in prostate cancer development, we generated and characterized a transgenic adenocarcinoma mouse prostate (TRAMP) model with a Znt7-null genetic background. TRAMP mice (TRAMP/Znt7(-/-) and TRAMP/Znt7(+/+)) were euthanized at 6, 8, 16, and 28 weeks of age for histopathological analysis of the prostates and for the presence of prostate tumors and metastasis. At 6 and 8 weeks of age, TRAMP/Znt7(-/-) mice displayed higher frequencies of low grade prostatic intraepithelial neoplasia (PIN) and high grade PIN, respectively, in the prostates than the age-matched TRAMP/Znt7(+/+) mice. At 16 weeks of age, 33% TRAMP/Znt7(-/-) mice had prostate tumors and one half of the 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 had prostate tumors. Furthermore, apoptosis was reduced in the prostates of TRAMP/Znt7(-/-) mice. In conclusion, a null-mutation of the Znt7 gene accelerates prostate tumor formation in TRAMP mice.
authors.affiliation: Genetics Graduate Group, University of California at Davis, 95616, United States.
authors.forename: Surapun
authors.initials: S
authors.lastname: Tepaamorndech
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Kirschke
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse; C472293:ZnT7 protein, mouse