A Myc-Driven in Vivo Model of Human Prostate Cancer
Annual rept. 15 Sep 2005-14 Sep 2006
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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The long-term goal of the work proposed here is to generate, characterize and interrogate human epithelial cell-based in vivo models of prostatic carcinogenesis. These models will allow an examination of processes involved in carcinogenesis, tumor growth and metastasis. Since the tumors are themselves of human origin hey represent an in vivo test bed to examine both tumor biology and the application of therapeutic agents. In the second year of funding we have made a thorough study of the profiles of metastatic spread of human prostatic epithelium from the sub-renal and orthotopic graft sites and have found that the orthotopic site shows spread patterns and mechanisms which closely profile the human disease and apparently result from similar migration routes. We have developed a novel method of intraductal orthotopic grafting which enhances the efficiency of tumorigenesis and metastasis at the orthotopic site. We have further explored the use of lower dose Myc expressing constructs and have investigated the combination of lower levels of Myc with other genes commonly changed in prostate cancer to make more clinically relevant models. Tet- regulated Myc constructs have been used to develop tumors with suitable profiles in mice.
- Anatomy and Physiology
- Medicine and Medical Research