Isolation of Genes Involved in Human Prostate Cancer Progression by Functional Expression Cloning

摘要

During phase I of this IDEA Award, we examined mechanisms of androgen independent prostate cancer progression using our LAPC xenograft model. Our focus was to identify genes and/or signaling pathways that might be responsible for androgen independent growth, through expression cloning. We have successfully identified several such candidates through screening xenografts and validated the activity of these candidates in xenograft models. Our current focus is to study two genes/pathways that were identified in this screen (the EGFR/Her2 pathway and the cathepsin D protease) as tools to create new transgenic models of prostate cancer. We are also developing a new transgenic model using the avian retrovirus receptor TVA that will allow us to introduce multiple transgenes into the prostate in a stepwise manner and to manipulate androgen levels without affecting transgene expression (as part of the Phase II grant).