Development of a Mouse Model for Prostate Cancer Imaging and Study of Disease Progression

摘要

Prostate carcinogenesis is a multi-step process resulting in the transformation of prostatic epithelial cells into invasive carcinoma and metastasis. In recent years, mouse models have emerged that recapitulate salient features of prostate carcinogenesis found in human disease. These models illuminate the molecular events that result in transformation and disease progression. In addition, mouse models can be used to identify molecular targets and test chemotherapeutic agents that may alter the course of disease. We have generated a new mouse model to further delineate targets are critical for cancer progression. This genetically engineered mouse is a cross between the TRAMP and PSCA-TVA transgenic mice. The resultant TRAMP-TVA breed develops prostate cancer epithelial cells that express a unique avian viral receptor (TVA). TRAMP-TVA mice are susceptible to infection by avian sarcoma leucosis viruses (ASLV) that carry specific genetic material that can target intracellular pathways. The prostate cells of these mice, therefore, are targets for specific gene transfer of imaging genes and small hairpin nuclear RNAs (shRNAs) resulting in knockdown of specific targets. TRAMP-TVA mice demonstrate PIN lesions at 8 weeks and develop adenocarcinoma at 6-15 months. We have been able to demonstrate PSCA-driven expression of the TVA viral receptor in these lesions. Orthotopic and intraperitoneal injection of virus containing the luciferase gene results in luminescence signal from infected prostate epithelial cells. Further development of this model will enable the effect of genetic alterations targeted to the prostate to be evaluated in the setting of an in vivo metastatic prostate cancer model.