Transgenic Models for Prostate Cancer
Annual summary rept. 1 Aug 1998-28 Jan 2003
CALIFORNIA UNIV LOS ANGELES DIV OF HEMATOLOGY/ONCOLOGY
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During phase II of this IDEA Award, our goal was to study genespathways implicated in prostate cancer progression using transgenic mouse models. Our efforts focused on creating transgenic models that express 1 of 4 different genes in the mouse prostate. All 4 genes were selected based on studies from our lab and others implicating these genes in human prostate cancer. These include Her-2neu, cathepsin D, Akt, and Myc. We were successful in generating each of the transgenic mice, and the phenotypes of 3 of them Cathepsin D, Akt, and Nyc have been fully characterized. Cathepsin D and Akt mice develop prostatic intraepithelial neoplasia PIN only, whereas Myc mice develop PIN that progresses to invasive prostatic adenocarcinoma. In addition, we created transgenic mice expressing the avian retrovirus receptor TVA to permit introduction of multiple transgenes into the prostate in a stepwise manner and to manipulate androgen levels without affecting transgene expression. We documented successful infection with avian retroviruses expressing marker genes CEP and are optimizing conditions for transfer of oncogenes. We also generated luciferase transgenic mice, which allow us to visualize the mouse prostate using optimal imaging tools.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research