RNA Interference Library Approach to Identifying Mechanisms of Ovarian Cancer Metastasis

摘要

Screens using RNAi have identified genes required for specific cellular processes including apoptosis, proliferation and tumorigenesis. Stable expression of a vector based short-hairpin RNA (shRNA) library allows one to screen human genes for their individual roles in specific biologic processes. Specifically we will use an shRNA library screen to identify known and novel metastasis suppressor genes in ovarian carcinoma. Our model will identify both metastasis suppressor genes as well as genes involved in suppression of intraperitoneal attachment and tumor growth. Using this approach we generated several ovarian cancer cell sub clones that exhibited metastatic intraperitoneal tumorigenesis a compared to vector or untransfected cell lines. These lines exhibited in vito selectable marker resistance and rederived intraperitoneal tumorigenesis in second pass validation studies.