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

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Annual rept. 1 Jan-31 Dec 2007

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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 test chemotherapeutic agents that may alter the course of disease. We have generated a new mouse model to further delineate targets that may halt cancer progression and lead to regression of disease. Crossing the TRAMP mouse with the PSCA-TVA transgenic mouse has resulted in the TRAMP-TVA mouse that is destined to develop prostate cancer and 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 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. 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 interference to be monitored non-invasively in mice. This approach will facilitate high throughput analysis of potential shRNA targets.ta

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  • Biochemistry
  • Medicine and Medical Research

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