Identification of Prostate Cancer Metastasis-Suppressor Genes Using Genomic shRNA Libraries

摘要

The so-called 'lethal phenotype' in prostate cancer (CaP) involves the recurrence of metastatic disease after androgen-ablation therapy. However, little is known regarding the genetics that control disease recurrence. Our proposed research was to screen for metastasis- inducing genes in LNCaP and LAPC-4 CaP cells using libraries expressing RNAi covering the entire human genome. We have infected the CaP cell lines with two librades a retrovirus library encoding validated shRNAs for 983 'cancer genes' and a lentivirus genomic shRNA library (GIPZ). We have identified cells with significantly increased capabilities for Matrigel invasion over spontaneous rates and we are now identifying and validating individual genes whose knockdown contributes to the increased invasive potential of CaP cells. In addition to potentially serving as clinically predictive biomarkers these genes will be useful in understanding the molecular events required for metastatic progression in CaP.