An Allograft Model of Androgen Independent Prostatic Neuroendocrine Carcinoma Derived From a Large Probasin Promoter-T Antigen Transgenic Mouse Line

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Abstract
Purpose: Animal models that mimic this hormone refractory prostate cancer may be useful for developing and testing novel treatment strategies. Materials and Methods: Using the prostate of the 12T-10 transgenic mouse an allograft model was established by transplantation into a nude mouse. To our knowledge we describe the first allograft model derived from the primary prostate tumor of a transgenic mouse. Results: The primary tumor progressed from high grade prostatic intraepithelial neoplasm to invasive, undifferentiated and metastatic cancer with loss of androgen receptor expression. After 10 passages in nude mice the allograft retained the same histological and immunohistochemical features as the primary tumors, including neuroendocrine differentiation. The allograft demonstrated androgen independent growth and metastases to liver and lung, paralleling tumor behavior in the original transgenic line. Cytogenetic characterization of the allograft revealed consistent chromosomal abnormalities for multiple in vivo passages. Conclusions: This allograft model may give insight into the mechanism by which human prostate cancer progresses to an androgen independent state and provide a system for testing drugs that can inhibit this disease.