Animal Core

Overview
The Animal Technology Core serves investigators through consultation, training, and implementation of procedures required for the proper and efficient use of transgenic models of prostate cancer and other in vivo models of prostatic research. As the careful use of animal models is indispensable to cutting-edge cancer research, almost all of the SPORE projects and pilot projects utilize the technical resources of this core. Its specific goals are to:

• Provide consultation services on mouse prostate and transgenic models of prostate carcinogenesis;
• Evaluate existing transgenic models of prostate cancer and recommend utilization of specific models most appropriate to the goals of the research project;
• Develop new transgenic models of prostate cancer as needed;
• Provide training and/or participate in the harvesting of individual lobes of the mouse prostate at all stages of development (neonatal to adult) and all stages of pathogenesis (normal to invasive cancer);
• Perform prostatic ductal microdissection;
• Perform injection of viral suspensions into mouse prostate, perform direct intra-ductal injection of viral suspensions and perform injection of viral suspensions into the internal iliac artery, which supplies the prostate;
• Perform subcutaneous and subrenal capsule grafting into host animals of prostatic carcinoma cell lines, transplantable mouse prostatic tumors, or human prostatic cancer xenografts;
• Perform neonatal rat prostate organ culture assay for testing monoclonal antibodies and anti-sense oligonucleotides for their ability to inhibit prostatic growth and differentiation;
• Develop and characterize rabbit monoclonal antibodies selectively reactive for human prostatic carcinoma cells or tumor stroma.

In the past year, the core has developed several tissue recombinant models of prostatic carcinogenesis in part through collaborations with the Balmain group. The prototypic model consists of rat UGM or SVM combined prostatic epithelium (PrE) derived from a tumor suppressor gene knockout mouse or a transgenic mouse. The host can be treated with testosterone plus estradiol (T+E) or untreated. Using the rat SVM+PrE model we have achieved PIN lesions using the following mutant prostatic epithelium: nkx3.1-/-, p53-/-, pten+/-, Rb-/-, p27+/-, pten-/-, telomerase-/-, pten+/-p53+/-, nkx3.1-/-p53-/-. The most severe lesions (high grade PIN) are seen at high incidence in any of the pten mutants. Only a few tissue recombinants exhibit invasion. The pten+/-p53+/- tissue recombinants show a consistent amplification of mouse chromosome 8.