Development of a Mouse Model for Prostate Cancer Imaging and Study of Disease Progression
Annual rept. 1 Jan-31 Dec 2006
CALIFORNIA UNIV LOS ANGELES
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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 to test chemotherapeutic agents that may alter the course of a disease. The authors have generated a new mouse model to further delineate molecular targets that may halt cancer progression andor lead to regression of metastatic disease. To repidly evaluate a variety of select target genes in the long-term, the authors have created a new transgenic mouse. Crossing the TRAMP mouse with the PSCA-TVA transgenic mouse has resulted in the TRAMP-TVA mouse, which allows for efficient and specific gene transfer of imaging genes into prostate epithelial cells that are destined to form cancer, and that expresses the avian viral receptor, TVA, on prostate cancer cells. This new transgenic mouse should enable specific gene transfer of imaging genes and small hairpin nuclear RNAs shRNAs resulting in knockdown of specific targets. TRAMP-TVA mice demonstrate prostatic cellular neoplasia PIN lesions at 8 weeks and develop adenocarcinoma at 6-15 months. The authors have been able to demonstrate PSCA-driven expression of the TVA viral receptor in these lesions. Intraperitoneal injection of virus containing the luciferase gene results in luminescence signal in the prostate. Further development of this model will enable the effect of target gene knockdown via RNA.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research