A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells

A transgenic mouse model of metastatic prostate cancer has been developed t hat is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of th e 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 mous e prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a we ek 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 tra nsformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.