Abstract

A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penerrant 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.

Original languageEnglish
Pages (from-to)15382-15387
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number26
DOIs
StatePublished - Dec 22 1998

Keywords

  • Prostatic intraepithelial neoplasia

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