title: A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells.
abstract: A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progresses rapidly to local invasion. Metastases to lymph nodes, liver, lung, and bone are common by 6 months. Tumorigenesis is not dependent on androgens. This model indicates that the neuroendocrine cell lineage of the prostate is exquisitely sensitive to transformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Garabedian
authors.forename: P A
authors.initials: PA
authors.lastname: Humphrey
authors.forename: J I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics; D023082:Defensins; D004195:Disease Models, Animal; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009490:Neurosecretory Systems / Q000378:metabolism / Q000473:pathology*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D011506:Proteins / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics
chemical_list: D000957:Antigens, Viral, Tumor; D023082:Defensins; D011506:Proteins; C107641:cryptdin 2; D019382:Human Growth Hormone