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  • Title: Lobe-specific lineages of carcinogenesis in the transgenic adenocarcinoma of mouse prostate and their responses to chemopreventive selenium.
    Author: Wang L, Zhang J, Zhang Y, Nkhata K, Quealy E, Liao JD, Cleary MP, Lü J.
    Journal: Prostate; 2011 Sep 15; 71(13):1429-40. PubMed ID: 21360561.
    Abstract:
    BACKGROUND: The transgenic adenocarcinoma of mouse prostate (TRAMP) model is by far the most practical transgenic model for preclinical prostate cancer chemoprevention studies. It is critical to characterize the prostate lobe-specificity of lesion lineages to consolidate the advantages of this model and minimize its limitations for chemoprevention studies. METHODS: We dissected dorsolateral (DLP), ventral (VP), and anterior prostate (AP) lobes, and macroscopic tumors from 90 male C57BL/6J TRAMP mice at 22-24 weeks of age (WOA) and analyzed lesions by histological, biochemical and proteomic approaches. To determine whether methylseleninic acid (MSeA) led to a deletion of initiated cells, we gave oral MSeA to TRAMP mice from 5 to 23 WOA or from 5 to 15 WOA and analyzed lesions at 23 WOA. RESULTS: All tumors (n = 18) were T-antigen(+), synaptophysin (SYP)(+), androgen-receptor(-), and E-cadherin(-) poorly differentiated neuroendocrine carcinomas (NE-Ca). They were traceable most frequently to VP (66.7%) and rarely to DLP (11.1%) and AP (5.6%) with an estimated life-time incidence of 1 out of 3 mice. In DLP, epithelial lesions ranged from mild-to-severe atypical hyperplasia, with T-antigen(+), SYP(-), androgen-receptor(+), and E-cadherin(+). Proteomic profiling revealed many molecular differences between VP and DLP. In MSeA experiment, 6 out of 19 (31.5%) mice developed NE-Ca in the control group, only 2 in each MSeA group of 17-18 mice (11.1-11.8%) bore a detectable NE-Ca. CONCLUSION: The C57BL/6J TRAMP mouse represents at least two lineages of prostate carcinogenesis. Chemoprevention studies should incorporate this knowledge for efficacy assessment and molecular target validations.
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